The DOI matches its Crossref record; 220 of the 227 references it cites were found in a registry or an index; 8 of the 385 sources its claims cite were checked for support.
Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Open accessAbstract
The most prevalent chronic neurodegenerative illness in the world is Alzheimer’s disease (AD). It results in mental symptoms including behavioral abnormalities and cognitive impairment, which have a substantial financial and psychological impact on the relatives of the patients. The review discusses various pathophysiological mechanisms contributing to AD, including amyloid beta, tau protein, inflammation, and other factors, while emphasizing the need for effective disease-modifying therapeutics that alter disease progression rather than merely alleviating symptoms. This review mainly covers medications that are now being studied in clinical trials or recently approved by the FDA that fall under the disease-modifying treatment (DMT) category, which alters the progression of the disease by targeting underlying biological mechanisms rather than merely alleviating symptoms. DMTs focus on improving patient outcomes by slowing cognitive decline, enhancing neuroprotection, and supporting neurogenesis. Additionally, the review covers amyloid-targeting therapies, tau-targeting therapies, neuroprotective therapies, and others. This evaluation specifically looked at studies on FDA-approved novel DMTs in Phase II or III development that were carried out between 2021 and 2024. A thorough review of the US government database identified clinical trials of biologics and small molecule drugs for 14 agents in Phase I, 34 in Phase II, and 11 in Phase III that might be completed by 2028.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review summarizes Alzheimer’s disease pathophysiology and disease-modifying therapies, focusing on amyloid-, tau-, and neuroprotective strategies and recent FDA-approved or clinical-stage agents. It reports the 2024 AD drug development pipeline and highlights challenges including disease heterogeneity, blood–brain barrier penetration, biomarkers, and regulation.
Key findings
- The 2024 AD drug development pipeline included 164 trials, of which 127 were testing possible treatments or medicines; 41% targeted disease-modifying small molecules and 34% targeted disease-modifying biological agents, with the remaining trials focused on cognitive or neuropsychiatric symptoms.
- A review of the US government clinical trials database identified disease-modifying biologic and small-molecule trials for 14 agents in Phase I, 34 in Phase II, and 11 in Phase III that might be completed by 2028. Section 3.2 separately reports Phase I: 26 trials assessing 25 agents; Phase II: 90 studies of 81 medicines; Phase III: 48 trials testing 32 medications.
- Lecanemab reduced total brain amyloid plaque burden versus placebo at 79 weeks, with a mean difference of −73.5 centiloids and −0.31 standardized uptake value ratio (SUVR) units; the treatment effect was dose- and exposure-dependent, and the study suggested a 20%–40% risk reduction in clinical symptom progression.
- Aducanumab showed inconsistent results in the Phase III EMERGE and ENGAGE trials; FDA expedited approval was based on the EMERGE trial’s amyloid reduction. Both aducanumab and lecanemab slowed cognitive decline and reduced amyloid plaques but were more likely to cause amyloid-related imaging abnormalities (ARIAs), especially ARIA-E with aducanumab.
Methods
- Narrative review of AD pathophysiology, disease-modifying therapeutic mechanisms, current treatments, clinical trials, and emerging therapies; no formal systematic review or meta-analysis is described.
- The evaluation focused on studies of FDA-approved novel DMTs in Phase II or III development conducted between 2021 and 2024, and a thorough review of the US government clinical trials database identified disease-modifying biologic and small-molecule agents across phases.
- Findings are presented in narrative text and in Tables 2 and 3, which summarize clinical trials of disease-modifying biological agents and disease-modifying small-molecule drugs, respectively.
Limitations
- Stated challenges include disease heterogeneity complicating diagnosis, treatment, and trial design; blood–brain barrier penetration limits drug delivery, with the text noting impermeability to 98% of small molecules and around 100% of large molecules in relevant quantities; lack of validated diagnostic biomarkers and low clinical diagnostic specificity can require larger trials and inclusion of “slow/no progressors”; regulatory obstacles include inconsistent review levels and restrictions on biobanking and repository research.
- The conclusion states that only a small percentage of AD patients benefit from the two currently approved DMTs, that more research comparing DMTs with diverse therapeutic targets and across patient groups is needed, and that natural compounds require clinical trials to verify safety and efficacy.
- Evident from the text: this is a narrative review without a described systematic search strategy, inclusion/exclusion criteria, or risk-of-bias assessment; trial-count figures in the abstract and Section 3.2 differ, which may reflect different database snapshots or definitions.
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Figures
![Figure 1 Pathophysiology of the AD hypothesis [8]. Reproduced with permission from Jifa Zhang, Yinglu Zhang, Jiaxing Wang, Yilin Xia, Jiaxian Zhang, and Lei Chen, in the journal Signal Transduction and Targeted Therapy; published by Springer Nature, 2024, licensed under CC BY 4.0.](/paper-figures/96e0143d1ef448fe8ee19762f0705b3a/recent-advances-in-therapeutics-for-the-treatment-of-alzheimers-disease-figure-1.jpg)
Verification
Claims the paper makes
142 Not checked yet · 7 Own interpretation · 2 Partly supported · 1 Supported · 1 Own result · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The AD risk is greatly increased by the APOE ε4 allele.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
- Supportedcites [42] Narayan, 2020, PICALM Rescues Endocytic Defects Caused by the Alzheimer’s Disease Risk Factor APOE4, Cell Rep. source
The Introduction describes APOE ε4 as a major genetic risk factor for late-onset Alzheimer’s disease and says that carriers of one APOE4 allele are 3–4 times more likely to develop AD than noncarriers. This supports the claim that the allele greatly increases AD risk. (LLM, conf=0.94)
- Supportedcites [43] Fu, 2023, The role of genetic risk factors of Alzheimer’s disease in synaptic dysfunction, Semin. Cell Dev. Biol. source
Section 1.2, “Astrocytic genes” (page not supplied), calls APOE the most significant genetic risk factor for AD and says APOE ε4 carriers are more susceptible to AD. This supports the claim that the allele greatly increases AD risk. (LLM, conf=0.92)
- Partly supportedcites [44] Flores-Cordero, J.A., Pérez-Pérez, A., Jiménez-Cortegana, C., Alba, G., Flores-Barragán, A., and Sánchez-Margalet, V. (2022). Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin. Int. J. Mol. Sci., 23. sourceExperimental — accuracy not yet measured
Section 6 identifies APOE4 as the best-known genetic variant associated with increased Alzheimer’s disease risk. It does not describe the size of that increase, so it does not establish the claim’s “greatly” qualifier. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the healthy aging human brain, amyloid-β plaques have the ability to cause persistent inflammation in microglia, which are the brain’s resident immune cells.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Partly supportedcites [202] Yang, 2020, TREM2 ectodomain and its soluble form in Alzheimer’s disease, J. Neuroinflamm. sourceExperimental — accuracy not yet measured
The “Microglial activation and innate immune system” section describes chronic neuroinflammation in Alzheimer’s disease and reports that some studies find protein overload induces an inflammatory response. It does not establish persistent plaque-caused microglial inflammation in the healthy aging human brain; it says the relationship between protein deposition and inflammation is conflicting. (LLM, conf=0.87)
- Partly supportedcites [203] Huang, W., Huang, J., Huang, N., and Luo, Y. (2023). The role of TREM2 in Alzheimer’s disease: From the perspective of Tau. Front. Cell Dev. Biol., 11. sourceExperimental — accuracy not yet measured
Section 2 (page unavailable) identifies TREM2 as a microglial receptor for Aβ, and Section 3 links microglial regulation to neuroinflammation in Alzheimer’s disease. Neither passage says that amyloid-β plaques cause persistent microglial inflammation in healthy aging human brains; that setting, duration, and causal claim are unsupported. (LLM, conf=0.78)
- Partly supportedcites [204] Shi, Q., Gutierrez, R.A., and Bhat, M.A. (2024). Microglia, Trem2, and Neurodegeneration. Neuroscientist, 10738584241254118. sourceExperimental — accuracy not yet measured
The Figure 3 caption in “Mechanisms Linking TREM2 Variants to AD” says that accumulating amyloid-β plaques during Alzheimer disease progression can lead to excessive microglial activation and release of proinflammatory factors. “Microglia—Specialized Neuroimmune Cells” identifies microglia as the brain’s resident immune cells and links chronic inflammation to neurodegenerative disease. The paper does not establish this plaque-driven persistent inflammation specifically in the healthy aging human brain. (LLM, conf=0.87)
- Partly supportedcites [205] Pocock, 2024, Microglia and TREM2, Neuropharmacology sourceExperimental — accuracy not yet measured
The paper’s discussion of TREM2 and NLRP3 inflammasome activation says that exposure to amyloid-β can activate an inflammasome and release proinflammatory cytokines. It does not establish that amyloid-β plaques cause persistent microglial inflammation in healthy aging human brains. The Conclusions identify microglia as immune cells of the brain. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“One example of this is rasagiline, which combines neuroprotective and amyloid-processing properties with monoamine oxidase B inhibition [217].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Supportedcites [217] Cummings, 2019, Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options, J. Alzheimer’s Dis. source
The TYPES OF COMBINATION THERAPIES section explicitly identifies rasagiline as an MAO B inhibitor with neuroprotective effects and effects on amyloid processing. The Phase II add-on and combination treatments section further describes its neuroprotective action and modulation of AβPP cleavage. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A thorough review of the US government database identified clinical trials of biologics and small molecule drugs for 14 agents in Phase I, 34 in Phase II, and 11 in Phase III that might be completed by 2028.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > Abstract
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The hydrophobic C-terminus of Aβ42 facilitates its aggregation and the formation of senile plaques.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Mutations in presenilin-1 (PS1) can promote Aβ accumulation through increased production and impaired autophagy functions.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“This hypothesis suggests that a reduction in the synthesis and release of ACh impairs its physiological functions, which are critical for learning, memory, and other cognitive processes.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“This hypothesis posits that various pathological factors, such as Aβ plaques, pro-inflammatory cytokines, and oxidative stress, activate microglia, the central nervous system’s innate immune cells. Upon activation, microglia undergo morphological changes and initiate a variety of inflammatory responses, which can lead to the release of pro-inflammatory mediators that exacerbate neurotoxicity.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The persistent activation of microglia may result in a failure to resolve inflammation, contributing to neuronal damage and the cognitive decline associated with AD [15,16].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“A person with one copy of this allele is more likely to be affected than a person with two copies [42,43,44].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
- Not checked yetcites [42] Narayan, 2020, PICALM Rescues Endocytic Defects Caused by the Alzheimer’s Disease Risk Factor APOE4, Cell Rep. source
- Not checked yetcites [43] Fu, 2023, The role of genetic risk factors of Alzheimer’s disease in synaptic dysfunction, Semin. Cell Dev. Biol. source
- Not checked yetcites [44] Flores-Cordero, J.A., Pérez-Pérez, A., Jiménez-Cortegana, C., Alba, G., Flores-Barragán, A., and Sánchez-Margalet, V. (2022). Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin. Int. J. Mol. Sci., 23. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 38
- It may state two separate claims as one. 57
In the paper
“AD is a progressive neurodegenerative disorder and the leading cause of dementia among older adults, characterized by a gradual decline in cognitive function, memory loss, and behavioral changes, ultimately leading to complete dependence on caregivers [7].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [7] Chen, Z.-R., Huang, J.-B., Yang, S.-L., and Hong, F.-F. (2022). Role of Cholinergic Signaling in Alzheimer’s Disease. Molecules, 27. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The tau protein hypothesis focuses on the hyperphosphorylation of tau protein leading to its detachment from microtubules, resulting in the formation of neurofibrillary tangles (NFTs) which are a hallmark of AD.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The glutamatergic hypothesis posits that dysregulation of glutamate, the main excitatory neurotransmitter in the central nervous system, plays a critical role in the pathogenesis of AD.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [10] Conway, 2020, Alzheimer’s disease: Targeting the glutamatergic system, Biogerontology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“However, the relationship between FAD mutations and Aβ levels is complex, and the plaque formation in sporadic AD is influenced by a dynamic imbalance between Aβ production and clearance mechanisms [11,12].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AChE inhibitors, such as donepezil, rivastigmine, and galantamine, have been developed as treatments based on this hypothesis, although their efficacy is limited and they do not halt disease progression [7,9].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The inflammatory hypothesis suggests that chronic neuroinflammation plays a significant role in the pathogenesis of AD.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The microbiota–gut–brain axis hypothesis suggests a bidirectional communication system between the gut and the brain, involving metabolic, endocrine, neural, and immune pathways.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [17] Wiatrak, B., Balon, K., Jawień, P., Bednarz, D., Jęśkowiak, I., and Szeląg, A. (2022). The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer’s Disease. Int. J. Mol. Sci., 23. source
- Not checked yetcites [18] Doifode, 2020, The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology, Pharmacol. Res. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The cholinergic hypothesis posits that the degeneration of cholinergic neurons, particularly in the basal forebrain, is a central feature of AD and is closely linked to cognitive decline.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The pathophysiological process of AD is multifaceted, involving several key hypotheses: the cholinergic, glutamatergic, amyloid, tau protein, inflammatory, microbiota–gut–brain axis, oxidative stress, metal ion, and abnormal autophagy hypotheses, as shown in the summary of AD pathophysiology in Figure 1 [8].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [8] Zhang, 2024, Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies, Signal Transduct. Target. Ther. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“This hyperphosphorylation promotes tau aggregation into paired helical filaments and NFTs, which correlate strongly with clinical symptoms of AD.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Dysbiosis, or disruption of the microbiota’s composition and functionality, can occur due to factors such as dietary changes, antibiotic use, psychosocial stress, or immune irregularities, leading to a compromised intestinal epithelial barrier.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [17] Wiatrak, B., Balon, K., Jawień, P., Bednarz, D., Jęśkowiak, I., and Szeląg, A. (2022). The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer’s Disease. Int. J. Mol. Sci., 23. source
- Not checked yetcites [18] Doifode, 2020, The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology, Pharmacol. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Aβ originates from the processing of the amyloid precursor protein (APP) through sequential cleavage by β-secretase and γ-secretase, resulting in various lengths of Aβ fragments, with Aβ40 and Aβ42 being predominant.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The amyloid hypothesis emphasizes that the accumulation of Aβ plaques in the brain is a central event in the pathogenesis of AD, leading to neurodegeneration and cognitive decline.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The decline in choline acetyltransferase (ChAT) activity, combined with the detrimental effects of amyloid beta (Aβ) on cholinergic signaling, leads to decreased ACh levels. Consequently, this reduction contributes to the cognitive deficits observed in AD patients.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, tau pathology is associated with neuroinflammation, as pro-inflammatory cytokines can increase tau transcription and activate inflammatory pathways that further exacerbate tau-related neurodegeneration [13,14].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Key contributors to oxidative stress in AD include mitochondrial dysfunction, which reduces the activities of essential enzymes and disrupts mitochondrial dynamics.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [19] Jurcau, 2020, Oxidative Stress in the Pathogenesis of Alzheimer’s Disease and Cerebrovascular Disease with Therapeutic Implications, CNS Neurol. Disord.—Drug Targets
- Not checked yetcites [20] Bai, 2022, Oxidative stress: The core pathogenesis and mechanism of Alzheimer’s disease, Ageing Res. Rev. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, exposure to air pollution may worsen neuroinflammation and cognitive decline [49,50].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
- Not checked yetcites [49] Attademo, 2020, Air Pollution as Risk Factor for Mental Disorders: In Search for a Possible Link with Alzheimer’s Disease and Schizophrenia, J. Alzheimer’s Dis. source
- Not checked yetcites [50] He, 2022, Impact of air pollution exposure on the risk of Alzheimer’s disease in China: A community-based cohort study, Environ. Res. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, sedentary lifestyles and bad dietary habits, such as consuming large amounts of carbs and saturated fats, have been connected to an increased risk [54,55,56,57].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
- Not checked yetcites [54] Gentreau, 2020, Refined carbohydrate-rich diet is associated with long-term risk of dementia and Alzheimer’s disease in apolipoprotein E ε4 allele carriers, Alzheimer’s Dement. source
- Not checked yetcites [55] Frausto, D.M., Forsyth, C.B., Keshavarzian, A., and Voigt, R.M. (2021). Dietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites. Front. Neurosci., 15. source
- Not checked yetcites [56] Ellouze, I., Sheffler, J., Nagpal, R., and Arjmandi, B. (2023). Dietary Patterns and Alzheimer’s Disease: An Updated Review Linking Nutrition to Neuroscience. Nutrients, 15. source
- Not checked yetcites [57] Khemka, 2023, Role of diet and exercise in aging, Alzheimer’s disease, and other chronic diseases, Ageing Res. Rev. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“AD is categorized into three stages: mild, moderate, and severe [24,25,26,27,28].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [24] Liew, 2021, Neuropsychiatric symptoms in early stage of Alzheimer’s and non-Alzheimer’s dementia, and the risk of progression to severe dementia, Age Ageing source
- Not checked yetcites [25] Cummings, 2021, The Role of Neuropsychiatric Symptoms in Research Diagnostic Criteria for Neurodegenerative Diseases, Am. J. Geriatr. Psychiatry source
- Not checked yetcites [26] Wiels, W.A., Wittens, M.M.J., Zeeuws, D., Baeken, C., and Engelborghs, S. (2021). Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia Due to AD: Relation with Disease Stage and Cognitive Deficits. Front. Psychiatry, 12. source
- Not checked yetcites [27] Devanand, 2022, Associations Between Neuropsychiatric Symptoms and Neuropathological Diagnoses of Alzheimer Disease and Related Dementias, JAMA Psychiatry source
- Not checked yetcites [28] Abbate, 2019, Signs and symptoms method in neuropsychology: A preliminary investigation of a standardized clinical interview for assessment of cognitive decline in dementia, Appl. Neuropsychol. Adult source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Dementia risk has been shown to rise with toxic exposure to heavy metals as lead, mercury, and aluminum [45,46,47,48].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
- Not checked yetcites [45] Antoniadou, 2020, Toxic Environmental Factors and their Association with the Development of Dementia: A Mini Review on Heavy Metals and Ambient Particulate Matter, Mater. Socio Medica source
- Not checked yetcites [46] Amirrad, 2017, Alzheimer’s Disease: Dawn of a New Era?, J. Pharm. Pharm. Sci. source
- Not checked yetcites [47] Islam, F., Shohag, S., Akhter, S., Islam, M.R., Sultana, S., Mitra, S., Chandran, D., Khandaker, M.U., Ashraf, G.M., and Idris, A.M. (2022). Exposure of metal toxicity in Alzheimer’s disease: An extensive review. Front. Pharmacol., 13. source
- Not checked yetcites [48] Rehman, Q., Rehman, K., and Akash, M.S.H. (2021). Heavy Metals and Neurological Disorders: From Exposure to Preventive Interventions. Emerging Contaminants and Associated Treatment Technologies, Springer International Publishing. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The abnormal autophagy hypothesis suggests that disruptions in the autophagy process are closely linked to the pathogenesis of AD.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [22] Curtis, 2019, Autophagy Dysfunction in Alzheimer’s Disease: Mechanistic Insights and New Therapeutic Opportunities, Biol. Psychiatry
- Not checked yetcites [23] Hamano, 2018, The Implications of Autophagy in Alzheimer’s Disease, Curr. Alzheimer Res. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The most well-known genes are those for presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP). Mutations in these genes can cause early-onset familial AD, which often manifests before the age of 65 [38].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
- Not checked yetcites [38] Prajapati, V., Shinde, S., Shrivastav, P., and Prajapati, B.G. (2024). New biologicals and biomaterials in the therapy of Alzheimer’s disease. Alzheimer’s Disease and Advanced Drug Delivery Strategies, Academic Press. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The two main gene categories associated with AD are deterministic and risk-factor genes [29,37].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“One of the main variables that causes AD is genetics. Certain genes that are inherited have been connected to the condition as risk factors.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AD risk factors include obesity, diabetes, high blood pressure, and high cholesterol [51,52,53].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
- Not checked yetcites [51] Yang, 2022, Association of Healthy Lifestyles with Risk of Alzheimer Disease and Related Dementias in Low-Income Black and White Americans, Neurology source
- Not checked yetcites [52] Heneghan, 2023, Modifiable Lifestyle Activities Affect Cognition in Cognitively Healthy Middle-Aged Individuals at Risk for Late-Life Alzheimer’s Disease, J. Alzheimer’s Dis. source
- Not checked yetcites [53] Shafighi, K., Villeneuve, S., Neto, P.R., Badhwar, A., Poirier, J., Sharma, V., Medina, Y.I., Silveira, P.P., Dube, L., and Glahn, D. (2023). Social isolation is linked to classical risk factors of Alzheimer’s disease-related dementias. PLoS ONE, 18. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The most common symptoms of AD are short-term memory loss, which is followed by a progressive impairment in both implicit and explicit memory. Those who have the condition also exhibit neuropsychiatric symptoms, and with time, they lose their ability to perform basic daily duties [24,25,26,27,28].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [24] Liew, 2021, Neuropsychiatric symptoms in early stage of Alzheimer’s and non-Alzheimer’s dementia, and the risk of progression to severe dementia, Age Ageing source
- Not checked yetcites [25] Cummings, 2021, The Role of Neuropsychiatric Symptoms in Research Diagnostic Criteria for Neurodegenerative Diseases, Am. J. Geriatr. Psychiatry source
- Not checked yetcites [26] Wiels, W.A., Wittens, M.M.J., Zeeuws, D., Baeken, C., and Engelborghs, S. (2021). Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia Due to AD: Relation with Disease Stage and Cognitive Deficits. Front. Psychiatry, 12. source
- Not checked yetcites [27] Devanand, 2022, Associations Between Neuropsychiatric Symptoms and Neuropathological Diagnoses of Alzheimer Disease and Related Dementias, JAMA Psychiatry source
- Not checked yetcites [28] Abbate, 2019, Signs and symptoms method in neuropsychology: A preliminary investigation of a standardized clinical interview for assessment of cognitive decline in dementia, Appl. Neuropsychol. Adult source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The emotional toll is high, causing worry, despair, and exhaustion in those who provide care [35,36].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [35] Vu, 2022, Impact of Alzheimer’s Disease on Caregivers in the United States, Health Psychol. Res. source
- Not checked yetcites [36] Kerwin, 2022, Alzheimer’s disease diagnosis and management: Perspectives from around the world, Alzheimer’s Dement. Diagn. Assess. Dis. Monit.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This hypothesis suggests that metal dyshomeostasis can lead to oxidative stress, which is linked to various pathological events in AD, such as amyloidosis and tauopathy.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [21] Chen, L.-L., Fan, Y.-G., Zhao, L.-X., Zhang, Q., and Wang, Z.-Y. (2022). The metal ion hypothesis of Alzheimer’s disease and the anti-neuroinflammatory effect of metal chelators. Bioorganic Chem., 131. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Patients with AD and their families, as well as the healthcare system, bear a heavy burden. Families must deal with social, economic, and emotional difficulties as the illness worsens.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.1. Pathophysiological Mechanisms and Symptoms of AD
What the sources say
- Not checked yetcites [35] Vu, 2022, Impact of Alzheimer’s Disease on Caregivers in the United States, Health Psychol. Res. source
- Not checked yetcites [36] Kerwin, 2022, Alzheimer’s disease diagnosis and management: Perspectives from around the world, Alzheimer’s Dement. Diagn. Assess. Dis. Monit.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Conversely, maintaining cardiovascular health, eating a balanced diet rich in antioxidants, and exercising frequently can all lower the incidence of AD [55,58].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 1. Introduction > 1.2. Causes and Factors of AD
What the sources say
- Not checked yetcites [55] Frausto, D.M., Forsyth, C.B., Keshavarzian, A., and Voigt, R.M. (2021). Dietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites. Front. Neurosci., 15. source
- Not checked yetcites [58] Zhu, 2021, Dietary fatty acids and risk for Alzheimer’s disease, dementia, and mild cognitive impairment: A prospective cohort meta-analysis, Nutrition source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Amyloidogenic proteins (Aβ) and tau are two examples of heat-shock proteins (HSPs) that can both promote and inhibit the aggregation of misfolded proteins [37,101].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics > 2.3. Mechanisms of Action
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [101] Yang, 2019, Heat Shock Protein Inspired Nanochaperones Restore Amyloid-β Homeostasis for Preventative Therapy of Alzheimer’s Disease, Adv. Sci. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“According to the amyloid cascade hypothesis, tau protein tangles and neuroinflammation are brought on by Aβ aggregation, which in turn leads to neuronal death and cognitive decline [90,91,92].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics > 2.3. Mechanisms of Action
What the sources say
- Not checked yetcites [90] Rabinovici, 2023, Amyloid-Targeting Monoclonal Antibodies for Alzheimer Disease, JAMA source
- Not checked yetcites [91] Fedele, E. (2023). Anti-Amyloid Therapies for Alzheimer’s Disease and the Amyloid Cascade Hypothesis. Int. J. Mol. Sci., 24. source
- Not checked yetcites [92] Qiao, 2024, Comparative Efficacy and Safety of Monoclonal Antibodies for Cognitive Decline in Patients with Alzheimer’s Disease: A Systematic Review and Network Meta-Analysis, CNS Drugs source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Research has indicated that tau pathology has a stronger correlation with cognitive deficits than Aβ plaques, indicating that treatment benefits from targeting tau may outweigh those from concentrating only on amyloid clearance [94,95].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics > 2.3. Mechanisms of Action
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Inadequate operation of these systems can lead to oxidative stress, mitochondrial dysfunction, and various other pathological conditions that damage the body, cause neuronal death, and exacerbate dementia.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics > 2.3. Mechanisms of Action
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [101] Yang, 2019, Heat Shock Protein Inspired Nanochaperones Restore Amyloid-β Homeostasis for Preventative Therapy of Alzheimer’s Disease, Adv. Sci. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The second generation of AChEIs, donepezil (labeled as 1, Figure 5), is an indanonebenzylpiperidine derivative that is authorized for the treatment of AD in all phases. By reversibly binding to acetylcholinesterase, it slows the hydrolysis of acetylcholine, increasing the concentration of ACh at synapses [106,107].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs
What the sources say
- Not checked yetcites [106] Cummings, 2021, New approaches to symptomatic treatments for Alzheimer’s disease, Mol. Neurodegener.
- Not checked yetcites [107] Eissa, 2022, Development of new Alzheimer’s disease drug candidates using donepezil as a key model, Arch. Der Pharm. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several clinical investigations focusing on Aβ have produced contradictory findings, casting doubt on the veracity of the amyloid theory in general.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics > 2.3. Mechanisms of Action
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DMTs are treatments that postpone, moderate, or even reverse the evolution of an illness by addressing its underlying cause.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics
What the sources say
- Not checked yetcites [6] Sperling, 2022, Meaningful benefits: A framework to assess disease-modifying therapies in preclinical and early Alzheimer’s disease, Alzheimer’s Res. Ther. source
- Not checked yetcites [59] Forester, 2020, Setbacks and Opportunities in Disease-Modifying Therapies in Alzheimer Disease, JAMA Psychiatry source
- Not checked yetcites [60] Morató, X., Pytel, V., Jofresa, S., Ruiz, A., and Boada, M. (2022). Symptomatic and Disease-Modifying Therapy Pipeline for Alzheimer’s Disease: Towards a Personalized Polypharmacology Patient-Centered Approach. Int. J. Mol. Sci., 23. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“It is a first-line medication for mild-to-severe AD that has a good efficacy and tolerability in improving behavioral symptoms, activities of daily living, and cognitive performance [110,112,113].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs
What the sources say
- Not checked yetcites [110] Manickam, 2022, Galantamine tethered hydrogel as a novel therapeutic target for streptozotocin-induced Alzheimer’s disease in Wistar rats, Curr. Res. Pharmacol. Drug Discov. source
- Not checked yetcites [112] Kaur, 2022, Galantamine: A Review Update, J. Drug Deliv. Ther. source
- Not checked yetcites [113] Santos, 2020, Use of galantamine in the treatment of Alzheimer’s disease and strategies to optimize its biosynthesis using the in vitro culture technique, Plant Cell Tissue Organ Cult. (PCTOC) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“DMTs are intended to delay the progression of long-term conditions such as AD and ultimately improve the patient’s quality of life [60].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics > 2.1. Definition of DMT
What the sources say
- Not checked yetcites [60] Morató, X., Pytel, V., Jofresa, S., Ruiz, A., and Boada, M. (2022). Symptomatic and Disease-Modifying Therapy Pipeline for Alzheimer’s Disease: Towards a Personalized Polypharmacology Patient-Centered Approach. Int. J. Mol. Sci., 23. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies have shown that Aβ buildup can start 15–20 years before clinical symptoms appear, indicating that therapy effectiveness may depend on early intervention [88,89].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics > 2.3. Mechanisms of Action
What the sources say
- Not checked yetcites [88] Panza, 2019, A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease, Nat. Rev. Neurol. source
- Not checked yetcites [89] Shi, M., Chu, F., Zhu, F., and Zhu, J. (2022). Impact of Anti-amyloid-β Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer’s Disease: A Focus on Aducanumab and Lecanemab. Front. Aging Neurosci., 14. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While lowering Aβ levels can decrease cognitive deterioration, not all patients will definitely see improved clinical outcomes from this strategy, according to certain research [86,93].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 2. Disease-Modifying Therapeutics > 2.3. Mechanisms of Action
What the sources say
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Memantine is safe and well-tolerated; it is used to treat moderate-to-severe AD alone or in combination with AChEI [124,125,126].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs
What the sources say
- Not checked yetcites [124] Marotta, G., Basagni, F., Rosini, M., and Minarini, A. (2020). Memantine Derivatives as Multitarget Agents in Alzheimer’s Disease. Molecules, 25. source
- Not checked yetcites [125] Turcu, 2022, Design, synthesis, and in vitro and in vivo characterization of new memantine analogs for Alzheimer’s disease, Eur. J. Med. Chem. source
- Not checked yetcites [126] Wu, 2021, Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer’s disease, Aging Cell source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The first disease-modifying medication for AD is a recombinant monoclonal antibody called aducanumab, also known by the brand name Aduhelm. It targets amyloid beta specifically [37]. It functions by lowering the quantity of amyloid deposits or brain plaques [130,131].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [130] Rahman, 2023, Aducanumab for the treatment of Alzheimer’s disease: A systematic review, Psychogeriatrics source
- Not checked yetcites [131] Wojtunik-Kulesza, K., Rudkowska, M., and Orzeł-Sajdłowska, A. (2023). Aducanumab—Hope or Disappointment for Alzheimer’s Disease. Int. J. Mol. Sci., 24. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Compared to oral pills, transdermal patches are more pleasant and provide a smaller dosage, which leads to fewer side effects.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs
What the sources say
- Not checked yetcites [119] Rompicherla, 2021, Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of Alzheimer’s disease, Naunyn-Schmiedeberg S Arch. Pharmacol. source
- Not checked yetcites [120] Guo, 2024, Rivastigmine nasal spray for the treatment of Alzheimer’s Disease: Olfactory deposition and brain delivery, Int. J. Pharm. source
- Not checked yetcites [121] Ezzat, S.M., Salem, M.A., Mahdy, N.M.E., and Ragab, M.F. (2021). Rivastigmine. Naturally Occurring Chemicals Against Alzheimer’s Disease, Elsevier. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The reduction in amyloid-beta brain plaques, a purported surrogate endpoint that indicates the “progression” of AD, and the encouraging clinical outcomes in one of the two pivotal Phase III trials were two of the factors cited for aducanumab’s expedited approval [130,134,135,136].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs
What the sources say
- Not checked yetcites [130] Rahman, 2023, Aducanumab for the treatment of Alzheimer’s disease: A systematic review, Psychogeriatrics source
- Not checked yetcites [134] Dunn, 2021, Approval of Aducanumab for Alzheimer Disease—The FDA’s Perspective, JAMA Intern. Med. source
- Not checked yetcites [135] Mullard, 2023, FDA approves second anti-amyloid antibody for Alzheimer disease, Nat. Rev. Drug Discov. source
- Not checked yetcites [136] Reardon, 2023, FDA approves Alzheimer’s drug lecanemab amid safety concerns, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CAD106, a further active Aβ immunotherapy, is presently undergoing clinical development. It involves administering multiple doses of the whole Aβ1–6 peptide linked to the ADP-Q carrier, a virus-like particle that generates high-titer anti-Aβ antibodies [140,141,153,154].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.1. Oral Immunotherapies or Small Molecules Containing DMTs
What the sources say
- Not checked yetcites [140] Bhadane, 2024, Immunotherapeutic approaches for Alzheimer’s disease: Exploring active and passive vaccine progress, Brain Res. source
- Not checked yetcites [141] Parrocha, 2022, Current peptide vaccine and immunotherapy approaches against Alzheimer’s disease, Pept. Sci. source
- Not checked yetcites [153] Riviere, 2023, Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes, Alzheimer’s Dement. source
- Not checked yetcites [154] Thakur, 2023, Attempts to Develop Vaccines Against Alzheimer’s Disease: A Systematic Review of Ongoing and Completed Vaccination Trials in Humans, Cureus
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Lecanemab (LEQEMBI, brand name), a different monoclonal antibody known as humanized immunoglobulin G1 (IgG1), which specifically targets aggregated forms of amyloid beta, was also given fast approval by the FDA earlier in the year [134,135,136].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs
What the sources say
- Not checked yetcites [134] Dunn, 2021, Approval of Aducanumab for Alzheimer Disease—The FDA’s Perspective, JAMA Intern. Med. source
- Not checked yetcites [135] Mullard, 2023, FDA approves second anti-amyloid antibody for Alzheimer disease, Nat. Rev. Drug Discov. source
- Not checked yetcites [136] Reardon, 2023, FDA approves Alzheimer’s drug lecanemab amid safety concerns, Nature source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Similar to other BACE-1 inhibitors, CNP520 (umibecestat (labeled as 11, Figure 5)) has been shown to reduce the burden of amyloid-beta plaques in preclinical animals; it is presently undergoing testing phases [157,166,167].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.1. Oral Immunotherapies or Small Molecules Containing DMTs
What the sources say
- Not checked yetcites [157] Piton, 2018, Alzheimer’s Disease: Advances in Drug Development, J. Alzheimer’s Dis. source
- Not checked yetcites [166] Machauer, 2021, Discovery of Umibecestat (CNP520): A Potent, Selective, and Efficacious β-Secretase (BACE1) Inhibitor for the Prevention of Alzheimer’s Disease, J. Med. Chem. source
- Not checked yetcites [167] Neumann, 2018, The BACE -1 inhibitor CNP 520 for prevention trials in Alzheimer’s disease, EMBO Mol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is authorized for use in mild-to-moderate Parkinson’s disease dementia and mild-to-moderate AD [116,117,118].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs
What the sources say
- Not checked yetcites [116] Ray, 2020, Rivastigmine modifies the α-secretase pathway and potentially early Alzheimer’s disease, Transl. Psychiatry source
- Not checked yetcites [117] Vicente-Zurdo, D., Rosales-Conrado, N., León-González, M.E., Brunetti, L., Piemontese, L., Pereira-Santos, A.R., Cardoso, S.M., Madrid, Y., Chaves, S., and Santos, M.A. (2022). Novel Rivastigmine Derivatives as Promising Multi-Target Compounds for Potential Treatment of Alzheimer’s Disease. Biomedicines, 10. source
- Not checked yetcites [118] Shamsi, 2020, Probing the interaction of Rivastigmine Tartrate, an important Alzheimer’s drug, with serum albumin: Attempting treatment of Alzheimer’s disease, Int. J. Biol. Macromol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Due to problems with binding efficiency, which show up as blue discolorations in urine, methylene blue (labeled as 12, Figure 5), which was also tried in Phase II clinical trials for mild-to-moderate AD (for suppressing tau aggregation), has drawn a lot of criticism [168,169,170].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.1. Oral Immunotherapies or Small Molecules Containing DMTs
What the sources say
- Not checked yetcites [168] Soeda, 2019, Methylene Blue Inhibits Formation of Tau Fibrils but not of Granular Tau Oligomers: A Plausible Key to Understanding Failure of a Clinical Trial for Alzheimer’s Disease, J. Alzheimer’s Dis. source
- Not checked yetcites [169] Berrocal, M., Caballero-Bermejo, M., Gutierrez-Merino, C., and Mata, A.M. (2019). Methylene Blue Blocks and Reverses the Inhibitory Effect of Tau on PMCA Function. Int. J. Mol. Sci., 20. source
- Not checked yetcites [170] How, 2018, Exploring the effects of methylene blue on amyloid fibrillogenesis of lysozyme, Int. J. Biol. Macromol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Phase II trials (90 studies, 81 medicines): these trials continue to investigate the drugs’ safety and efficacy.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [183] Cummings, 2024, Alzheimer’s disease drug development pipeline: 2024, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [184] Huang, L.-K., Kuan, Y.-C., Lin, H.-W., and Hu, C.-J. (2023). Clinical trials of new drugs for Alzheimer disease: A 2020–2023 update. J. Biomed. Sci., 30. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The tyrosine kinase inhibitor saracatinib (AZD0530 (labeled as 14, Figure 5)) is undergoing Phase II trials [174,175,176] and has been demonstrated to improve memory in transgenic mice models of AD.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.1. Oral Immunotherapies or Small Molecules Containing DMTs
What the sources say
- Not checked yetcites [174] Fagiani, 2020, Targeting dementias through cancer kinases inhibition, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [175] Ramos, R., and Vale, N. (2024). Dual Drug Repurposing: The Example of Saracatinib. Int. J. Mol. Sci., 25. source
- Not checked yetcites [176] Tridente, G., Jana, A., Nath, A., and Ashraf, G.M. (2023). Protein kinase inhibitors as therapeutics in neurodegenerative and psychiatric disorders. Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders, Academic Press. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In particular, a mean difference of −73.5 centiloides and −0.31 standardized uptake value ratio (SUVR) units was found between the lecanemab and placebo treatment groups.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [187] Mukhopadhyay, 2021, A Primer on the Evolution of Aducanumab: The First Antibody Approved for Treatment of Alzheimer’s Disease, J. Alzheimer’s Dis. source
- Not checked yetcites [188] Swanson, 2021, A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody, Alzheimer’s Res. Ther. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PDE4 inhibitors, which are oral small compounds that selectively inhibit PDE4, an enzyme involved in controlling cAMP levels, include roflumilast (15, Figure 5), which may lessen inflammation and increase neuronal survival [177,178,179,180].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.1. Oral Immunotherapies or Small Molecules Containing DMTs
What the sources say
- Not checked yetcites [177] Wang, 2020, The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice, Int. J. Neuropsychopharmacol. source
- Not checked yetcites [178] Sugin, 2020, Roflumilast: A potential drug for the treatment of cognitive impairment?, Neurosci. Lett. source
- Not checked yetcites [179] Hu, 2019, Synthesis and evaluation of clioquinol-rolipram/roflumilast hybrids as multitarget-directed ligands for the treatment of Alzheimer’s disease, Eur. J. Med. Chem. source
- Not checked yetcites [180] Hasan, 2022, Roflumilast Reduces Pathological Symptoms of Sporadic Alzheimer’s Disease in Rats Produced by Intracerebroventricular Streptozotocin by Inhibiting NF-κB/BACE-1 Mediated Aβ Production in the Hippocampus and Activating the cAMP/BDNF Signalling Pathway, Neurotox. Res. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Of these trials, 41% look into disease-modifying small molecule medications, 34% look into biological agents that change disease, and the remaining trials focus on treatments that improve cognitive function or address neuropsychiatric symptoms linked to ADs [68,70,71,182,183,184].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [68] Cummings, 2022, Alzheimer’s disease drug development pipeline: 2022, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [70] Cummings, 2020, Alzheimer’s disease drug development pipeline: 2020, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [71] Cummings, 2023, Alzheimer’s disease drug development pipeline: 2023, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [182] Cummings, 2021, Alzheimer’s disease drug development pipeline: 2021, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [183] Cummings, 2024, Alzheimer’s disease drug development pipeline: 2024, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [184] Huang, L.-K., Kuan, Y.-C., Lin, H.-W., and Hu, C.-J. (2023). Clinical trials of new drugs for Alzheimer disease: A 2020–2023 update. J. Biomed. Sci., 30. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The most recent list of studies was provided by the 2024 AD drug development pipeline, which includes 164 trials (of which 127 are exploring possible treatments or medicines).”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [68] Cummings, 2022, Alzheimer’s disease drug development pipeline: 2022, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [70] Cummings, 2020, Alzheimer’s disease drug development pipeline: 2020, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [71] Cummings, 2023, Alzheimer’s disease drug development pipeline: 2023, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [182] Cummings, 2021, Alzheimer’s disease drug development pipeline: 2021, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [183] Cummings, 2024, Alzheimer’s disease drug development pipeline: 2024, Alzheimer’s Dement. Transl. Res. Clin. Interv. source
- Not checked yetcites [184] Huang, L.-K., Kuan, Y.-C., Lin, H.-W., and Hu, C.-J. (2023). Clinical trials of new drugs for Alzheimer disease: A 2020–2023 update. J. Biomed. Sci., 30. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The BBB is impermeable to 98% of small molecules and around 100% of large molecules in relevant quantities.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [193] Conrado, 2020, Challenges in Alzheimer’s Disease Drug Discovery and Development: The Role of Modeling, Simulation, and Open Data, Clin. Pharmacol. Ther. source
- Not checked yetcites [194] Abduljawad, A.A., Elawad, M.A., Elkhalifa, M.E.M., Ahmed, A., Hamdoon, A.A.E., Salim, L.H.M., Ashraf, M., Ayaz, M., Hassan, S.S.U., and Bungau, S. (2022). Alzheimer’s Disease as a Major Public Health Concern: Role of Dietary Saponins in Mitigating Neurodegenerative Disorders and Their Underlying Mechanisms. Molecules, 27. source
- Not checked yetcites [195] Ribba, B. (2023). Reinforcement learning as an innovative model-based approach: Examples from precision dosing, digital health and computational psychiatry. Front. Pharmacol., 13. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This phenomenon is most likely caused by uncertainties in AD pathophysiology, such as the lack of validated diagnostic biomarkers and the low specificity of clinical diagnosis.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, the treatment impact increased in a dose- and exposure-dependent manner; a 25% AUC therapy was probably superior to a placebo by >0.64.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [187] Mukhopadhyay, 2021, A Primer on the Evolution of Aducanumab: The First Antibody Approved for Treatment of Alzheimer’s Disease, J. Alzheimer’s Dis. source
- Not checked yetcites [188] Swanson, 2021, A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody, Alzheimer’s Res. Ther. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“One of the regulatory obstacles in creating DMTs for AD is the insufficient knowledge and ability of regional regulatory organizations, in addition to post-study medication administration and sustained treatment supply.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [196] Ndebele, 2014, Regulatory Challenges Associated with Conducting Multicountry Clinical Trials in Resource-Limited Settings, JAIDS J. Acquir. Immune Defic. Syndr. source
- Not checked yetcites [197] Alemayehu, 2018, Barriers for conducting clinical trials in developing countries—A systematic review, Int. J. Equity Health source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The goal of tau treatments is to prevent tau from aggregating and spreading.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [198] Sinsky, J., Pichlerova, K., and Hanes, J. (2021). Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies. Int. J. Mol. Sci., 22. source
- Not checked yetcites [199] Alquezar, C., Arya, S., and Kao, A.W. (2021). Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation. Front. Neurol., 11. source
- Not checked yetcites [200] Yang, J., Zhi, W., and Wang, L. (2024). Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review. Molecules, 29. source
- Not checked yetcites [201] Sigurdsson, 2018, Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls1, J. Alzheimer’s Dis. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“While both aducanumab and lecanemab slowed cognitive decline and reduced amyloid plaques, they were more likely to cause amyloid-related imaging abnormalities (ARIAs), which are thought to be the most significant side effect of both drugs.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [92] Qiao, 2024, Comparative Efficacy and Safety of Monoclonal Antibodies for Cognitive Decline in Patients with Alzheimer’s Disease: A Systematic Review and Network Meta-Analysis, CNS Drugs source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, there are several review levels with conflicting results and different guidelines for participant reimbursement for trial-related injuries.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 3. AD Current Treatment Drugs > 3.2. Recent DMT’s Clinical Trials
What the sources say
- Not checked yetcites [196] Ndebele, 2014, Regulatory Challenges Associated with Conducting Multicountry Clinical Trials in Resource-Limited Settings, JAIDS J. Acquir. Immune Defic. Syndr. source
- Not checked yetcites [197] Alemayehu, 2018, Barriers for conducting clinical trials in developing countries—A systematic review, Int. J. Equity Health source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Even more targeted strategies are being developed to enhance neurotransmitter activity.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“PSEN1 and PSEN2 mutations, which are closely associated with early-onset AD and impact the γ-secretase cleavage products, such as Aβ, are important genetic factors.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [213] AlMansoori, M.E., Jemimah, S., Abuhantash, F., and AlShehhi, A. (2024). Predicting early Alzheimer’s with blood biomarkers and clinical features. Sci. Rep., 14. source
- Not checked yetcites [214] Kesu, S.M.R., Sinha, N., and Ramasangu, H. (2024). Cellular Automata Framework for Dementia Classification Using Explainable AI. Eng. Proc., 68. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TREM2 agonists are being investigated as potential therapeutic agents since they reduce inflammation and encourage amyloid-beta microglial phagocytosis [202,203,204,205].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [202] Yang, 2020, TREM2 ectodomain and its soluble form in Alzheimer’s disease, J. Neuroinflamm. source
- Not checked yetcites [203] Huang, W., Huang, J., Huang, N., and Luo, Y. (2023). The role of TREM2 in Alzheimer’s disease: From the perspective of Tau. Front. Cell Dev. Biol., 11. source
- Not checked yetcites [204] Shi, Q., Gutierrez, R.A., and Bhat, M.A. (2024). Microglia, Trem2, and Neurodegeneration. Neuroscientist, 10738584241254118. source
- Not checked yetcites [205] Pocock, 2024, Microglia and TREM2, Neuropharmacology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finding preventative drugs derived from conventional herbal remedies is one approach to treating AD.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 5. Prospects for the Future of Phytochemical Treatment of AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“These systems have demonstrated notable advances in diagnostic performance, particularly in radiology.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [213] AlMansoori, M.E., Jemimah, S., Abuhantash, F., and AlShehhi, A. (2024). Predicting early Alzheimer’s with blood biomarkers and clinical features. Sci. Rep., 14. source
- Not checked yetcites [216] Forloni, 2020, Alzheimer’s disease: From basic science to precision medicine approach, BMJ Neurol. Open source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“This allows for disease stratification and may even facilitate an earlier diagnosis [214,215].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [214] Kesu, S.M.R., Sinha, N., and Ramasangu, H. (2024). Cellular Automata Framework for Dementia Classification Using Explainable AI. Eng. Proc., 68. source
- Not checked yetcites [215] Arafah, A., Khatoon, S., Rasool, I., Khan, A., Rather, M.A., Abujabal, K.A., Faqih, Y.A.H., Rashid, H., Rashid, S.M., and Ahmad, S.B. (2023). The Future of Precision Medicine in the Cure of Alzheimer’s Disease. Biomedicines, 11. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Certain dysregulated proteostasis, dysregulated circadian rhythms, inflammation, oxidative stress, tau proteinopathies, and dysregulated metabolism may all be treated therapeutically with some DMTs.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 6. Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Combination therapy is another example; it targets different pharmacologic targets (such as tau and amyloid) or targets pathways sequentially by using successive combinations.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [217] Cummings, 2019, Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options, J. Alzheimer’s Dis. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“New advances in synthetic biology and genomics open up new avenues for discovering and using the medicinal properties of plants.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 5. Prospects for the Future of Phytochemical Treatment of AD
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“These markers provide information about the underlying pathophysiology of AD and are crucial for detecting the disease, especially in those who have memory problems.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [214] Kesu, S.M.R., Sinha, N., and Ramasangu, H. (2024). Cellular Automata Framework for Dementia Classification Using Explainable AI. Eng. Proc., 68. source
- Not checked yetcites [215] Arafah, A., Khatoon, S., Rasool, I., Khan, A., Rather, M.A., Abujabal, K.A., Faqih, Y.A.H., Rashid, H., Rashid, S.M., and Ahmad, S.B. (2023). The Future of Precision Medicine in the Cure of Alzheimer’s Disease. Biomedicines, 11. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These AI systems are very good at finding patterns, assessing large volumes of data, and forecasting the likelihood of developing diseases.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [213] AlMansoori, M.E., Jemimah, S., Abuhantash, F., and AlShehhi, A. (2024). Predicting early Alzheimer’s with blood biomarkers and clinical features. Sci. Rep., 14. source
- Not checked yetcites [216] Forloni, 2020, Alzheimer’s disease: From basic science to precision medicine approach, BMJ Neurol. Open source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AI systems have been approved by the US Food and Drug Administration (FDA) for enhancing medical imaging assessments, including the identification of suspicious lesions [37,213,216].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [37] Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25. source
- Not checked yetcites [213] AlMansoori, M.E., Jemimah, S., Abuhantash, F., and AlShehhi, A. (2024). Predicting early Alzheimer’s with blood biomarkers and clinical features. Sci. Rep., 14. source
- Not checked yetcites [216] Forloni, 2020, Alzheimer’s disease: From basic science to precision medicine approach, BMJ Neurol. Open source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Another type of combination therapy is represented by multifunctional compounds, which incorporate several activities or targets into a single medication.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [217] Cummings, 2019, Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options, J. Alzheimer’s Dis. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“It becomes a comprehensive care paradigm when pharmacological therapies are combined with lifestyle changes, cognitive training, and psychosocial support.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [220] Strac, 2021, Personalizing the Care and Treatment of Alzheimer’s Disease: An Overview, Pharmacogenom. Pers. Med.
- Not checked yetcites [221] Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate-Armand, C., Yen, F.T., and Arab-Tehrany, E. (2022). Alzheimer’s Disease: Treatment Strategies and Their Limitations. Int. J. Mol. Sci., 23. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The search for new leads in AD treatment could be fruitful if herbal remedies are evaluated for lead chemicals based on their physicochemical properties and predicted BBB actions.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 5. Prospects for the Future of Phytochemical Treatment of AD
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A DMT with a particular therapeutic target may be more effective than other DMTs with different targets due to the complex and all-encompassing pathogenesis of AD, particularly if the therapeutic target of the DMT being administered aligns with the most salient pathological findings of the subpopulation.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 6. Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Pharmacodynamic agent combinations for AD may consist of DMTs, which change the course of the disease, or symptomatic medicines, which reduce the symptoms without changing the course of the disease.”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [217] Cummings, 2019, Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options, J. Alzheimer’s Dis. source
- Not checked yetcites [218] Horani, 2015, Anticancer Prodrugs—Three Decades of Design, World J. Pharm. Pharm. Sci.
- Not checked yetcites [219] Dudchenko, 2024, Combination Drug Therapy for the Management of Alzheimer’s Disease, Russ. J. Geriatr. Med. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This approach is adaptable enough to be customized for every single patient, ensuring optimal treatment outcomes [220,221].”
§ Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease > 4. Future Directions and Emerging Therapies in DMT
What the sources say
- Not checked yetcites [220] Strac, 2021, Personalizing the Care and Treatment of Alzheimer’s Disease: An Overview, Pharmacogenom. Pers. Med.
- Not checked yetcites [221] Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate-Armand, C., Yen, F.T., and Arab-Tehrany, E. (2022). Alzheimer’s Disease: Treatment Strategies and Their Limitations. Int. J. Mol. Sci., 23. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
Only a small percentage of AD patients benefit from the two DMTs currently approved for therapy.
“Only a small percentage of AD patients benefit from the two DMTs that are currently approved for therapy.”
The paper relies on this without support.
Several natural compounds have demonstrated potential for treating AD in both in vitro and in vivo studies.
“Nevertheless, several natural compounds have demonstrated potential for treating AD in both in vitro and in vivo studies.”
The paper relies on this without support.
Humans and animals in studies differ physiologically.
“because humans and animals in studies differ physiologically”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Several drugs focus on symptom management such as cholinesterase inhibitors (ChEIs): rivastigmine, donepezil, galantamine, and tacrine work by increasing ACh levels, improving cognition and memory, though they do not alter the disease’s progression.”
From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Current treatments for AD, including cholinesterase inhibitors and memantine, offer limited symptom relief, especially in the early to moderate stages, but do not halt disease progression or address the underlying neurodegeneration.”
From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [9]
Experimental — accuracy not yet measured
Citations
Cites
1 retracted
Hasan, N., Zameer, S., Najmi, A. K., Parvez, S., & Akhtar, M. (2022) · Neurotoxicity Research · doi:10.1007/s12640-022-00482-x · Cited by 17 · cited 1×
“PDE4 inhibitors, which are oral small compounds that selectively inhibit PDE4, an enzyme involved in controlling cAMP levels, include roflumilast ( 15 , Figure 5), which may lessen inflammation and increase neuronal survival [177–180].”
BackgroundRetractedLecanemab in early Alzheimer's disease
van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2212948 · Cited by 5,678 · cited 1×
“There is insufficient safety or efficacy information on starting treatment sooner or later than in the conducted studies [137–139].”
BackgroundScheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465
Comprehensive Review on Alzheimer’s Disease: Causes and Treatment
Breijyeh, Z., & Karaman, R. (2020) · Molecules · doi:10.3390/molecules25245789 · Cited by 2,789 · cited 10×
“DMTs consist of three primary components: therapy, sick-Molecules ness, and modification [37,59].”
BackgroundInfluentialSelf-citationThe Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · cited 1×
“However, the relationship between FAD mutations and A β levels is complex, and the plaque formation in sporadic AD is influenced by a dynamic imbalance between A β production and clearance mechanisms [11,12].”
BackgroundZhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138 · cited 1×
“…process of AD is multifaceted, involving several key hypotheses: the cholinergic, glutamatergic, amyloid, tau protein, inflammatory, microbiota–gut– brain axis, oxidative stress, metal ion, and abnormal autophagy hypotheses, as shown in the summary of AD pathophysiology in Figure 1 [8].”
BackgroundTau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · cited 3×
“This change in emphasis has made room for novel treatment strategies meant to lessen the consequences of tau-related neurodegeneration [13,95].”
BackgroundClinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group
Dubois, B., Villain, N., Frisoni, G. B., Rabinovici, G. D., Sabbagh, M., Cappa, S., Bejanin, A., Bombois, S., Epelbaum, S., Teichmann, M., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00066-1 · Cited by 1,051
Simpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044
Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988 · cited 1×
“While lowering A β levels can decrease cognitive deterioration, not all patients will definitely see improved clinical outcomes from this strategy, according to certain research [86,93].”
BackgroundCurrent and Future Treatments in Alzheimer Disease: An Update
Yiannopoulou, K. G., & Papageorgiou, S. G. (2020) · Journal of Central Nervous System Disease · doi:10.1177/1179573520907397 · Cited by 966 · cited 1×
“Donepezil, galantamine, and rivastigmine are the cholinesterase inhibitors that are most frequently prescribed [102–106].”
BackgroundA critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · cited 1×
“Studies have shown that A β buildup can start 15–20 years before clinical symptoms appear, indicating that therapy effectiveness may depend on early intervention [88,89].”
BackgroundRole of Cholinergic Signaling in Alzheimer’s Disease
Chen, Z.-R., Huang, J.-B., Yang, S.-L., & Hong, F.-F. (2022) · Molecules · doi:10.3390/molecules27061816 · Cited by 922 · cited 2×
“AD is a progressive neurodegenerative disorder and the leading cause of dementia among older adults, characterized by a gradual decline in cognitive function, memory loss, and behavioral changes, ultimately leading to complete dependence on caregivers [7].”
BackgroundSwanson, C. J., Zhang, Y., Dhadda, S., Wang, J., Kaplow, J., Lai, R. Y. K., Lannfelt, L., Bradley, H., Rabe, M., Koyama, A., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00813-8 · Cited by 847 · cited 1×
“The study also suggested at week 79 that a risk reduction of 20% to 40% be applied to the advancement of clinical symptoms [187,188].”
BackgroundOxidative stress: The core pathogenesis and mechanism of Alzheimer’s disease
Bai, R., Guo, J., Ye, X.-Y., Xie, Y., & Xie, T. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101619 · Cited by 813
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Karran, E., & De Strooper, B. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00391-w · Cited by 742 · cited 2×
“Enhancing neuroprotection is one of DMTs’ main objectives [74].”
BackgroundAlzheimer’s disease drug development pipeline: 2024
Cummings, J., Zhou, Y., Lee, G., Zhong, K., Fonseca, J., & Cheng, F. (2024) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12465 · Cited by 702 · cited 2×
“Phase III trials, including 48 trials that tested 32 medications [37,183,184].”
BackgroundAlzheimer's Disease: Treatment Strategies and Their Limitations.
Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F. T., & Arab-Tehrany, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213954 · Cited by 689 · cited 1×
“This approach is adaptable enough to be customized for every single patient, ensuring optimal treatment outcomes [220,221].”
BackgroundInteraction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease
Zhang, H., Wei, W., Zhao, M., Ma, L., Jiang, X., Pei, H., Cao, Y., & Li, H. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.57078 · Cited by 689 · cited 1×
“Research indicates that lowering amyloid levels may help to mitigate the neurodegeneration and cognitive impairment associated with the disease [82–84].”
BackgroundRandomized trial of verubecestat for mild-to-moderate Alzheimer's disease
Egan, M. F., Kost, J., Tariot, P. N., Aisen, P. S., Cummings, J. L., Vellas, B., Sur, C., Mukai, Y., Voss, T., Furtek, C., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1706441 · Cited by 685 · cited 1×
“In order to decrease the synthesis of amyloid beta, β - secretase inhibitors (BACE inhibitors) such lanabecestat (labeled as 8 , Figure 5) [157,161,162], verubecestat (labeled as 9 , Figure 5) [157,163,164], and atabecestat (labeled as 10 , Figure 5) target the enzyme Bace-1 [157,165].”
BackgroundAlzheimer’s disease drug development pipeline: 2022
Cummings, J., Lee, G., Nahed, P., Kambar, M. E. Z. N., Zhong, K., Fonseca, J., & Taghva, K. (2022) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12295 · Cited by 665
Alzheimer’s Disease: Epidemiology and Clinical Progression
Tahami Monfared, A. A., Byrnes, M. J., White, L. A., & Zhang, Q. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00338-8 · Cited by 629
Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options
Cummings, J. L., Tong, G., & Ballard, C. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-180766 · Cited by 588 · cited 2×
“As an illustration, ongoing clinical trials combine novel DMT-or symptomatic-based treatments with standard-of-care medications (such as memantine or cholinesterase inhibitors) [217–219].”
BackgroundMethodAlzheimer’s disease drug development pipeline: 2020
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2020) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12050 · Cited by 557 · cited 3×
“These tables represent agents in the three phases of disease-modifying agents’ development for AD [38,46,68,70,71,157,182,183,189].”
BackgroundAlzheimer’s disease: Recent treatment strategies
Vaz, M., & Silvestre, S. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173554 · Cited by 547
Randomized trial of verubecestat for prodromal Alzheimer's disease
Egan, M. F., Kost, J., Voss, T., Mukai, Y., Aisen, P. S., Cummings, J. L., Tariot, P. N., Vellas, B., van Dyck, C. H., Boada, M., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812840 · Cited by 545 · cited 1×
“In order to decrease the synthesis of amyloid beta, β - secretase inhibitors (BACE inhibitors) such lanabecestat (labeled as 8 , Figure 5) [157,161,162], verubecestat (labeled as 9 , Figure 5) [157,163,164], and atabecestat (labeled as 10 , Figure 5) target the enzyme Bace-1 [157,165].”
BackgroundNeuroprotective Effect of Antioxidants in the Brain
Lee, K. H., Cha, M., & Lee, B. H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197152 · Cited by 543 · cited 1×
“Neuroprotective drugs may be able to postpone the development of more severe symptoms by preserving the health and function of neurons [76,77].”
BackgroundAlzheimer’s disease drug development pipeline: 2021
Cummings, J., Lee, G., Zhong, K., Fonseca, J., & Taghva, K. (2021) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12179 · Cited by 539 · cited 2×
“These tables represent agents in the three phases of disease-modifying agents’ development for AD [38,46,68,70,71,157,182,183,189].”
BackgroundKnopman, D. S., Jones, D. T., & Greicius, M. D. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12213 · Cited by 524 · cited 1×
“In spite of this, the FDA granted expedited approval on the grounds of the EMERGE trial’s documented decrease in amyloid levels [132,185–187].”
BackgroundTau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516 · cited 1×
“But a lot of these methods have had difficulties in the clinic, frequently because of problems with toxicity or ineffectiveness [95,98].”
BackgroundAlzheimer’s disease drug development pipeline: 2023
Cummings, J., Zhou, Y., Lee, G., Zhong, K., Fonseca, J., & Cheng, F. (2023) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12385 · Cited by 477 · cited 3×
“These therapies aim to preserve neuronal connectivity and function by concentrating on specific pathological pathways [69–71].”
BackgroundSöderberg, L., Johannesson, M., Nygren, P., Laudon, H., Eriksson, F., Osswald, G., Möller, C., & Lannfelt, L. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01308-6 · Cited by 459
Trial of solanezumab in preclinical Alzheimer's disease
Sperling, R. A., Donohue, M. C., Raman, R., Rafii, M. S., Johnson, K., Masters, C. L., van Dyck, C. H., Iwatsubo, T., Marshall, G. A., Yaari, R., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2305032 · Cited by 429 · cited 1×
“Clinical trials have investigated many anti-A β antibodies, such as solanezumab [145,146], bapineuzumab [147–149], and aducanuamb.”
BackgroundMultimodal deep learning for Alzheimer's disease dementia assessment
Qiu, S., Miller, M. I., Joshi, P. S., Lee, J. C., Xue, C., Ni, Y., Wang, Y., De Anda-Duran, I., Hwang, P. H., Cramer, J. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31037-5 · Cited by 420 · cited 1×
“The pharmaceutical industry has been closely monitoring the advancement of AD therapy in an attempt to progress neurological disease treatment [1,2].”
BackgroundBiomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies
Zetterberg, H., & Bendlin, B. B. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0721-9 · Cited by 408 · cited 1×
“While symptomatic therapies may provide immediate relief from pain or fatigue, DMTs specifically work to change the immune response or repair brain damage [64,65].”
BackgroundBarriers for conducting clinical trials in developing countries—A systematic review
Alemayehu, C., Mitchell, G., & Nikles, J. (2018) · International Journal for Equity in Health · doi:10.1186/s12939-018-0748-6 · Cited by 406 · cited 1×
“Moreover, biobanking and repository research are being scrutinized and restricted more harshly [196,197].”
BackgroundTau-targeting therapies for Alzheimer disease: Current status and future directions
Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00883-2 · Cited by 371 · cited 1×
“Research has indicated that tau pathology has a stronger correlation with cognitive deficits than A β plaques, indicating that treatment benefits from targeting tau may outweigh those from concentrating only on amyloid clearance [94,95].”
BackgroundReview on Alzheimer’s Disease: Inhibition of Amyloid Beta and Tau Tangle Formation
Ashrafian, H., Zadeh, E. H., & Khan, R. H. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.11.192 · Cited by 368 · cited 1×
“Research indicates that lowering amyloid levels may help to mitigate the neurodegeneration and cognitive impairment associated with the disease [82–84].”
BackgroundAlquezar, C., Arya, S., & Kao, A. W. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.595532 · Cited by 367
Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease
Arnsten, A. F. T., Datta, D., Del Tredici, K., & Braak, H. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12192 · Cited by 361 · cited 2×
“Additionally, tau pathology is associated with neuroinflammation, as pro-inflammatory cytokines can increase tau transcription and activate inflammatory pathways that further exacerbate tau-related neurodegeneration [13,14].”
BackgroundThe impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology
Doifode, T., Giridharan, V. V., Generoso, J. S., Bhatti, G., Collodel, A., Schulz, P. E., Forlenza, O. V., & Barichello, T. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2020.105314 · Cited by 347 · cited 1×
“Such inflammation may enable inflammatory mediators to cross the blood–brain barrier (BBB) and affect microglia, exacerbating neuroinflammation, which ultimately contributes to neuronal degeneration and damage [17,18].”
BackgroundTwo phase 3 trials of gantenerumab in early Alzheimer's disease
Bateman, R. J., Smith, J., Donohue, M. C., Delmar, P., Abbas, R., Salloway, S., Wojtowicz, J., Blennow, K., Bittner, T., Black, S. E., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2304430 · Cited by 314 · cited 1×
“Additionally, gantenerumab [150–152] and crenezumab [92,147,149] were examined.”
BackgroundJeremic, D., Jiménez-Díaz, L., & Navarro-López, J. D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101496 · Cited by 306 · cited 1×
“The main goal of these treatments is to lessen or completely eradicate beta-amyloid (A β ) plaques in the brain, which are thought to be a major factor in the development of AD [85–87].”
BackgroundDhillon, S. (2021) · Drugs · doi:10.1007/s40265-021-01569-z · Cited by 293
A resurrection of aducanumab for Alzheimer's disease
Schneider, L. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30480-6 · Cited by 286 · cited 1×
“Every four weeks, an intravenous (IV) dose is administered [132,133].”
BackgroundRole of tau protein in Alzheimer’s disease: The prime pathological player
Muralidar, S., Ambi, S. V., Sekaran, S., Thirumalai, D., & Palaniappan, B. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.07.327 · Cited by 278 · cited 3×
“Additionally, tau pathology is associated with neuroinflammation, as pro-inflammatory cytokines can increase tau transcription and activate inflammatory pathways that further exacerbate tau-related neurodegeneration [13,14].”
BackgroundShi, M., Chu, F., Zhu, F., & Zhu, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.870517 · Cited by 275 · cited 1×
“Studies have shown that A β buildup can start 15–20 years before clinical symptoms appear, indicating that therapy effectiveness may depend on early intervention [88,89].”
BackgroundClinical trials of new drugs for Alzheimer disease: a 2020–2023 update
Huang, L.-K., Kuan, Y.-C., Lin, H.-W., & Hu, C.-J. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00976-6 · Cited by 252 · cited 2×
“Phase III trials, including 48 trials that tested 32 medications [37,183,184].”
BackgroundApproval of Aducanumab for Alzheimer Disease—The FDA’s Perspective
Dunn, B., Stein, P., & Cavazzoni, P. (2021) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2021.4607 · Cited by 246 · cited 3×
“Lecanemab (LEQEMBI, brand name), a different monoclonal antibody known as humanized immunoglobulin G1 (IgG1), which specifically targets aggregated forms of amyloid beta, was also given fast approval by the FDA earlier in the year [134–136].”
BackgroundResultAmyloidosis in Alzheimer’s Disease: Pathogeny, Etiology, and Related Therapeutic Directions
Ma, C., Hong, F., & Yang, S. (2022) · Molecules · doi:10.3390/molecules27041210 · Cited by 243 · cited 1×
“However, the relationship between FAD mutations and A β levels is complex, and the plaque formation in sporadic AD is influenced by a dynamic imbalance between A β production and clearance mechanisms [11,12].”
BackgroundTherapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives
Pardo-Moreno, T., González-Acedo, A., Rivas-Domínguez, A., García-Morales, V., García-Cozar, F. J., Ramos-Rodríguez, J. J., & Melguizo-Rodríguez, L. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061117 · Cited by 239
New approaches to symptomatic treatments for Alzheimer’s disease
Cummings, J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00424-9 · Cited by 226 · cited 3×
“By re-versibly binding to acetylcholinesterase, it slows the hydrolysis of acetylcholine, increasing the concentration of ACh at synapses [106,107].”
BackgroundSu, F., Bai, F., & Zhang, Z. (2016) · Neuroscience Bulletin · doi:10.1007/s12264-016-0055-4 · Cited by 221 · cited 2×
“Cholinesterase inhibitors and NMDA receptor antagonists are the only two categories of medications that are prescribed to address symptoms [208].”
BackgroundTau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · cited 1×
“First, there is evidence that tau vaccinations may slow the disease’s course by reducing tau protein accumulation [198–201].”
BackgroundGenetics of Alzheimer’s disease: where we are, and where we are going
Bellenguez, C., Grenier-Boley, B., & Lambert, J.-C. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.11.024 · Cited by 215 · cited 1×
“According to studies, having these gene mutations practically guarantees that a person will develop the sickness [39–41].”
BackgroundObesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin
Flores-Cordero, J. A., Pérez-Pérez, A., Jiménez-Cortegana, C., Alba, G., Flores-Barragán, A., & Sánchez-Margalet, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095202 · Cited by 212 · cited 1×
“A person with one copy of this allele is more likely to be affected than a person with two copies [42–44].”
BackgroundChen, L.-L., Fan, Y.-G., Zhao, L.-X., Zhang, Q., & Wang, Z.-Y. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.106301 · Cited by 200 · cited 1×
“Overall, the accumulation and mismanagement of metal ions are closely associated with the neurodegenerative processes observed in AD [21].”
BackgroundSynaptic Plasticity, Dementia and Alzheimer Disease
Skaper, S. D., Facci, L., Zusso, M., & Giusti, P. (2017) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527316666170113120853 · Cited by 192 · cited 1×
“Examples of medications that may improve synaptic function include those that allosterically increase the M1 muscarinic acetylcholine receptor [209,210].”
BackgroundAmyloid-Related Imaging Abnormalities and β-Amyloid-Targeting Antibodies: A Systematic Review.
Filippi, M., Cecchetti, G., Spinelli, E. G., Vezzulli, P., Falini, A., & Agosta, F. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2021.5205 · Cited by 189 · cited 1×
“The main goal of these treatments is to lessen or completely eradicate beta-amyloid (A β ) plaques in the brain, which are thought to be a major factor in the development of AD [85–87].”
BackgroundDuara, R., & Barker, W. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01185-z · Cited by 187 · cited 1×
“More work has to be conducted to take this variability into account in order to improve the results of AD clinical trials [190–192].”
BackgroundReimagining cholinergic therapy for Alzheimer’s disease
Giacobini, E., Cuello, A. C., & Fisher, A. (2022) · Brain · doi:10.1093/brain/awac096 · Cited by 187 · cited 1×
“AChE inhibitors, such as donepezil, rivastigmine, and galantamine, have been developed as treatments based on this hypothesis, although their efficacy is limited and they do not halt disease progression [7,9].”
BackgroundRole of Aducanumab in the Treatment of Alzheimer’s Disease: Challenges and Opportunities
Vaz, M., Silva, V., Monteiro, C., & Silvestre, S. (2022) · Clinical Interventions in Aging · doi:10.2147/cia.s325026 · Cited by 183 · cited 2×
“Every four weeks, an intravenous (IV) dose is administered [132,133].”
BackgroundAlzheimer’s disease: Targeting the glutamatergic system
Conway, M. E. (2020) · Biogerontology · doi:10.1007/s10522-020-09860-4 · Cited by 180 · cited 1×
“…dysregulation can cause neuronal swelling and initiate various calcium-dependent processes, including the production of reactive oxygen species (ROS), disruption of mitochondrial function, and activation of necrotic or apoptotic pathways, ultimately resulting in excitotoxic damage to neurons [10].”
BackgroundFDA approves Alzheimer’s drug lecanemab amid safety concerns
Reardon, S. (2023) · Nature · doi:10.1038/d41586-023-00030-3 · Cited by 180 · cited 3×
“Lecanemab (LEQEMBI, brand name), a different monoclonal antibody known as humanized immunoglobulin G1 (IgG1), which specifically targets aggregated forms of amyloid beta, was also given fast approval by the FDA earlier in the year [134–136].”
BackgroundResultDetection and treatment of Alzheimer’s disease in its preclinical stage
Rafii, M. S., & Aisen, P. S. S. (2023) · Nature Aging · doi:10.1038/s43587-023-00410-4 · Cited by 179
Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting
Campanella, C., Pace, A., Bavisotto, C. C., Marzullo, P., Marino, A., Buscemi, S., & Piccionello, A. P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092603 · Cited by 177 · cited 1×
“Molecular chaperones can be classified as either external (clustered proteins, such alpha-macroglobulin and clustering) or intracellular (heat shock proteins, such as Hsp40, Hsp60, Hsp70, Hsp90, Hsp100, and Hsp110) [37,99,100].”
BackgroundThe BACE‐1 inhibitor CNP520 for prevention trials in Alzheimer's disease
Neumann, U., Ufer, M., Jacobson, L. H., Rouzade‐Dominguez, M., Huledal, G., Kolly, C., Lüönd, R. M., Machauer, R., Veenstra, S. J., Hurth, K., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201809316 · Cited by 177 · cited 1×
“Similar to other BACE-1 inhibitors, CNP520 (umibeces-tat (labeled as 11 , Figure 5)) has been shown to reduce the burden of amyloid-beta plaques in preclinical animals; it is presently undergoing testing phases [157,166,167].”
BackgroundInflammatory pathways in Alzheimer’s disease mediated by gut microbiota
Qian, X.-H., Song, X.-X., Liu, X.-L., Chen, S.-D., & Tang, H.-D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101317 · Cited by 153 · cited 1×
“The persistent activation of microglia may result in a failure to resolve inflammation, contributing to neuronal damage and the cognitive decline associated with AD [15,16].”
BackgroundHaass, C., & Selkoe, D. (2022) · PLOS Biology · doi:10.1371/journal.pbio.3001694 · Cited by 145 · cited 2×
“Lowering amyloid levels may help to lessen the disease’s related neurodegeneration and cognitive impairment, according to research [73,74].”
BackgroundDetecting the Stages of Alzheimer’s Disease with Pre-trained Deep Learning Architectures
Savaş, S. (2021) · Arabian Journal for Science and Engineering · doi:10.1007/s13369-021-06131-3 · Cited by 140
Autophagy Dysfunction in Alzheimer’s Disease: Mechanistic Insights and New Therapeutic Opportunities
Di Meco, A., Curtis, M. E., Lauretti, E., & Praticò, D. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.008 · Cited by 133 · cited 1×
“These defects may arise from genetic factors, reduced expression of related proteins, and impaired vesicular transportation, ultimately resulting in the accumulation of damaged organelles, such as dysfunctional mitochondria [22,23].”
BackgroundThe Future of Precision Medicine in the Cure of Alzheimer’s Disease
Arafah, A., Khatoon, S., Rasool, I., Khan, A., Rather, M. A., Abujabal, K. A., Faqih, Y. A. H., Rashid, H., Rashid, S. M., Bilal Ahmad, S., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11020335 · Cited by 133 · cited 1×
“This allows for disease stratification and may even facilitate an earlier diagnosis [214,215].”
BackgroundTang, B., Wang, Y., & Ren, J. (2023) · Ibrain · doi:10.1002/ibra.12098 · Cited by 129 · cited 1×
“The neurotoxicity seen in AD patients is caused by the glutaminergic system being overactivated, which is inhibited by memantine (labeled as 4 , Figure 5), an NMDAR low-affinity uncompetitive antagonist [37,122–124].”
BackgroundGenetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126
Staging of Alzheimer’s disease: past, present, and future perspectives
Therriault, J., Zimmer, E. R., Benedet, A. L., Pascoal, T. A., Gauthier, S. G., & Rosa‐Neto, P. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.05.008 · Cited by 123
Alzheimer’s Disease, Inflammation, and the Role of Antioxidants
Sinyor, B., Mineo, J., & Ochner, C. (2020) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-200171 · Cited by 120 · cited 1×
“The persistent activation of microglia may result in a failure to resolve inflammation, contributing to neuronal damage and the cognitive decline associated with AD [15,16].”
BackgroundDisease-Modifying Therapies for Alzheimer’s Disease: More Questions than Answers
Golde, T. E. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01201-2 · Cited by 119 · cited 2×
“This shift in focus is crucial for treating progressive illnesses because it addresses both the disease’s symptoms and the underlying issues that cause it to worsen [61,65–67].”
BackgroundTreatments for Alzheimer's disease emerge
Selkoe, D. J. (2021) · Science · doi:10.1126/science.abi6401 · Cited by 117
TREM2 ectodomain and its soluble form in Alzheimer’s disease
Yang, J., Fu, Z., Zhang, X., Xiong, M., Meng, L., & Zhang, Z. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01878-2 · Cited by 113 · cited 1×
“TREM2 agonists are being investigated as potential therapeutic agents since they reduce inflammation and encourage amyloid-beta microglial phagocytosis [202–205].”
BackgroundTimmers, M., Streffer, J. R., Russu, A., Tominaga, Y., Shimizu, H., Shiraishi, A., Tatikola, K., Smekens, P., Börjesson-Hanson, A., Andreasen, N., et al. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0415-6 · Cited by 112 · cited 1×
“In order to decrease the synthesis of amyloid beta, β - secretase inhibitors (BACE inhibitors) such lanabecestat (labeled as 8 , Figure 5) [157,161,162], verubecestat (labeled as 9 , Figure 5) [157,163,164], and atabecestat (labeled as 10 , Figure 5) target the enzyme Bace-1 [157,165].”
BackgroundMallah, K., Couch, C., Borucki, D. M., Toutonji, A., Alshareef, M., & Tomlinson, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02021 · Cited by 105 · cited 2×
“Based on how they work, DMTs can be divided into a number of categories [37,76,83].”
BackgroundDevanand, D. P., Lee, S., Huey, E. D., & Goldberg, T. E. (2022) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.4363 · Cited by 105
Aducanumab for the treatment of Alzheimer’s disease: A systematic review
Rahman, A., Hossen, M. A., Chowdhury, M. F. I., Bari, S., Tamanna, N., Sultana, S. S., Haque, S. N., Al Masud, A., & Saif‐Ur‐Rahman, K. M. (2023) · Psychogeriatrics · doi:10.1111/psyg.12944 · Cited by 104 · cited 2×
“The reduction in amyloid-beta brain plaques, a purported surrogate endpoint that indicates the “progres-sion” of AD, and the encouraging clinical outcomes in one of the two pivotal Phase III trials were two of the factors cited for aducanumab’s expedited approval [130,134–136].”
BackgroundResultDietary Patterns and Alzheimer’s Disease: An Updated Review Linking Nutrition to Neuroscience
Ellouze, I., Sheffler, J., Nagpal, R., & Arjmandi, B. (2023) · Nutrients · doi:10.3390/nu15143204 · Cited by 104
Anti-Amyloid Therapies for Alzheimer’s Disease and the Amyloid Cascade Hypothesis
Fedele, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914499 · Cited by 102
Yang, H., Li, X., Zhu, L., Wu, X., Zhang, S., Huang, F., Feng, X., & Shi, L. (2019) · Advanced Science · doi:10.1002/advs.201901844 · Cited by 98 · cited 1×
“Amyloidogenic proteins (A β ) and tau are two examples of heat-shock proteins (HSPs) that can both promote and inhibit the aggregation of misfolded proteins [37,101].”
BackgroundThe Role of Neuropsychiatric Symptoms in Research Diagnostic Criteria for Neurodegenerative Diseases
Cummings, J. (2021) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2020.07.011 · Cited by 96
Rani, V., Verma, R., Kumar, K., & Chawla, R. (2023) · Current Research in Pharmacology and Drug Discovery · doi:10.1016/j.crphar.2022.100149 · Cited by 93 · cited 1×
“Treatment options for neuroinflammation associated with AD have been investigated, including IL-1 β antagonists such as canakinumab [206–208].”
BackgroundRivastigmine modifies the α-secretase pathway and potentially early Alzheimer’s disease
Ray, B., Maloney, B., Sambamurti, K., Karnati, H. K., Nelson, P. T., Greig, N. H., & Lahiri, D. K. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0709-x · Cited by 91 · cited 3×
“ACh metabolism is inhibited by rivastigmine ( 3 , Figure 5), a pseudo-irreversible inhibitor of AChE and butyrylcholinesterase (BuChE) [114–116].”
BackgroundTau immunotherapies: Lessons learned, current status and future considerations
Sandusky-Beltran, L. A., & Sigurdsson, E. M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108104 · Cited by 90 · cited 1×
“Passive immunization with monoclonal antibodies and active immunization techniques that encourage the body’s immune system to generate its own antibodies against tau are two examples of different immunotherapeutic treatments [96,97].”
BackgroundEvaluation of Rivastigmine in Alzheimer’s Disease
Nguyen, K. T., Hoffman, H. L., Chakkamparambil, B., & Grossberg, G. T. (2020) · Neurodegenerative Disease Management · doi:10.2217/nmt-2020-0052 · Cited by 89 · cited 1×
“ACh metabolism is inhibited by rivastigmine ( 3 , Figure 5), a pseudo-irreversible inhibitor of AChE and butyrylcholinesterase (BuChE) [114–116].”
BackgroundRole of diet and exercise in aging, Alzheimer’s disease, and other chronic diseases
Khemka, S., Reddy, A., Garcia, R. I., Jacobs, M., Reddy, R. P., Roghani, A. K., Pattoor, V., Basu, T., Sehar, U., & Reddy, P. H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102091 · Cited by 88 · cited 1×
“Furthermore, sedentary lifestyles and bad dietary habits, such as consuming large amounts of carbs and saturated fats, have been connected to an increased risk [54–57].”
BackgroundDrug development for Alzheimer’s disease: Review
Lao, K., Ji, N., Zhang, X., Qiao, W., Tang, Z., & Gou, X. (2019) · Journal of drug targeting · doi:10.1080/1061186x.2018.1474361 · Cited by 86 · cited 1×
“Tideglusib (NP-031112 (labeled as 13 , Figure 5)), an inhibitor of GSK3 β , targets tau hyperphosphorylation, which is required for the development of tau tangles [171–173].”
BackgroundRompicherla, S. K. L., Arumugam, K., Bojja, S. L., Kumar, N., & Rao, C. M. (2021) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-021-02096-0 · Cited by 86 · cited 1×
“Since AD patients have memory and swallowing issues that make it difficult for them to take oral medications as prescribed, transdermal patches are the best way to administer rivastigmine to these patients [119–121].”
BackgroundSoeda, Y., Saito, M., Maeda, S., Ishida, K., Nakamura, A., Kojima, S., & Takashima, A. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-181001 · Cited by 84 · cited 1×
“Due to problems with binding efficiency, which show up as blue discolorations in urine, methylene blue (labeled as 12 , Figure 5), which was also tried in Phase II clinical trials for mild-to-moderate AD (for suppressing tau aggregation), has drawn a lot of criticism [168–170].”
BackgroundWang, H., Zhang, F.-F., Xu, Y., Fu, H.-R., Wang, X.-D., Wang, L., Chen, W., Xu, X.-Y., Gao, Y.-F., Zhang, J.-G., et al. (2020) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaa048 · Cited by 84 · cited 1×
“PDE4 inhibitors, which are oral small compounds that selectively inhibit PDE4, an enzyme involved in controlling cAMP levels, include roflumilast ( 15 , Figure 5), which may lessen inflammation and increase neuronal survival [177–180].”
BackgroundExposure of metal toxicity in Alzheimer’s disease: An extensive review
Islam, F., Shohag, S., Akhter, S., Islam, M. R., Sultana, S., Mitra, S., Chandran, D., Khandaker, M. U., Ashraf, G. M., Idris, A. M., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.903099 · Cited by 83
Preparing for disease-modifying therapies in Alzheimer's disease
Belder, C. R. S., Schott, J. M., & Fox, N. C. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00274-0 · Cited by 83 · cited 1×
“Based on their mechanisms of action, these treatments can be divided into several categories, including immunomodulatory medications, neuroprotective medications, and others that target specific pathways connected to disease processes [61–63].”
BackgroundJeremic, D., Navarro‐López, J. D., & Jiménez‐Díaz, L. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102012 · Cited by 82 · cited 2×
“Clinical trials have investigated many anti-A β antibodies, such as solanezumab [145,146], bapineuzumab [147–149], and aducanuamb.”
BackgroundAmyloid-Targeting Monoclonal Antibodies for Alzheimer Disease
Rabinovici, G. D., & La Joie, R. (2023) · JAMA · doi:10.1001/jama.2023.11703 · Cited by 80 · cited 1×
“According to the amyloid cascade hypothesis, tau protein tangles and neuroinflammation are brought on by A β aggregation, which in turn leads to neuronal death and cognitive decline [90–92].”
BackgroundRepurposed agents in the Alzheimer’s disease drug development pipeline
Bauzon, J., Lee, G., & Cummings, J. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00662-x · Cited by 77 · cited 1×
“Amyloid-beta buildup in the brain is believed to be crucial for the onset and progression of AD, and certain DMTs target this accumulation [70–72].”
BackgroundGalantamine-Memantine combination in the treatment of Alzheimer's disease and beyond
Koola, M. M. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2020.113409 · Cited by 77
Sigurdsson, E. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179937 · Cited by 76 · cited 1×
“First, there is evidence that tau vaccinations may slow the disease’s course by reducing tau protein accumulation [198–201].”
BackgroundChowdhury, S., & Chowdhury, N. S. (2023) · International Journal of Immunopathology and Pharmacology · doi:10.1177/03946320231209839 · Cited by 76 · cited 1×
“There is insufficient safety or efficacy information on starting treatment sooner or later than in the conducted studies [137–139].”
BackgroundPICALM Rescues Endocytic Defects Caused by the Alzheimer’s Disease Risk Factor APOE4
Narayan, P., Sienski, G., Bonner, J. M., Lin, Y.-T., Seo, J., Baru, V., Haque, A., Milo, B., Akay, L. A., Graziosi, A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108224 · Cited by 75
Shamsi, A., Mohammad, T., Anwar, S., Alajmi, M. F., Hussain, A., Hassan, M. I., Ahmad, F., & Islam, A. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.01.134 · Cited by 73 · cited 1×
“It is authorized for use in mild-to-moderate Parkinson’s disease dementia and mild-to-moderate AD [116–118].”
BackgroundAducanumab—Hope or Disappointment for Alzheimer’s Disease
Wojtunik-Kulesza, K., Rudkowska, M., & Orzeł-Sajdłowska, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054367 · Cited by 73 · cited 1×
“It functions by lowering the quantity of amyloid deposits or brain plaques [130,131].”
BackgroundAssunção, S. S., Sperling, R. A., Ritchie, C., Kerwin, D. R., Aisen, P. S., Lansdall, C., Atri, A., & Cummings, J. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-00984-y · Cited by 71 · cited 2×
“These novel strategies aim to both drastically alter the illness’s trajectory and cure its symptoms, which might make a big difference in the battle against this debilitating condition [5,6].”
BackgroundRole of GSK-3β Inhibitors: New Promises and Opportunities for Alzheimer’s Disease
Shri, S. R., Manandhar, S., Nayak, Y., & Pai, K. S. R. (2023) · Advanced Pharmaceutical Bulletin · doi:10.34172/apb.2023.071 · Cited by 71
Microglia, Trem2, and Neurodegeneration
Shi, Q., Gutierrez, R. A., & Bhat, M. A. (2025) · The Neuroscientist · doi:10.1177/10738584241254118 · Cited by 69
Advances on Therapeutic Strategies for Alzheimer’s Disease: From Medicinal Plant to Nanotechnology
Hassan, N. A., Alshamari, A. K., Hassan, A. A., Elharrif, M. G., Alhajri, A. M., Sattam, M., & Khattab, R. R. (2022) · Molecules · doi:10.3390/molecules27154839 · Cited by 68 · cited 1×
“The pharmaceutical industry has been closely monitoring the advancement of AD therapy in an attempt to progress neurological disease treatment [1,2].”
BackgroundSelective Secretase Targeting for Alzheimer’s Disease Therapy
Miranda, A., Montiel, E., Ulrich, H., & Paz, C. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201027 · Cited by 66 · cited 1×
“This includes γ -secretase inhibitors, such as tarenflurbil ( 7 , Figure 5) [155,156], avagacestat (labeled as 6 , Figure 5) [157,158], and semagacestat ( 5 , Figure 5) [159,160].”
BackgroundMukhopadhyay, S., & Banerjee, D. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215065 · Cited by 66 · cited 2×
“In spite of this, the FDA granted expedited approval on the grounds of the EMERGE trial’s documented decrease in amyloid levels [132,185–187].”
BackgroundTargeting aging and age-related diseases with vaccines
Wu, R., Sun, F., Zhang, W., Ren, J., & Liu, G.-H. (2024) · Nature Aging · doi:10.1038/s43587-024-00597-0 · Cited by 66 · cited 1×
“While lowering A β levels can decrease cognitive deterioration, not all patients will definitely see improved clinical outcomes from this strategy, according to certain research [86,93].”
BackgroundGenetics of Alzheimer’s disease: An East Asian perspective
Miyashita, A., Kikuchi, M., Hara, N., & Ikeuchi, T. (2023) · Journal of Human Genetics · doi:10.1038/s10038-022-01050-z · Cited by 64 · cited 1×
“According to studies, having these gene mutations practically guarantees that a person will develop the sickness [39–41].”
BackgroundAbduljawad, A. A., Elawad, M. A., Elkhalifa, M. E. M., Ahmed, A., Hamdoon, A. A. E., Salim, L. H. M., Ashraf, M., Ayaz, M., Hassan, S. S. U., & Bungau, S. (2022) · Molecules · doi:10.3390/molecules27206804 · Cited by 63
From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology
Toader, C., Dobrin, N., Brehar, F.-M., Popa, C., Covache-Busuioc, R.-A., Glavan, L.-A., Costin, H. P., Bratu, B.-G., Corlatescu, A.-D., Popa, A. A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216119 · Cited by 63 · cited 1×
“For this reason, there are still problems associated with this illness that scientists and physicians encounter globally [3,4].”
BackgroundYang, J., Zhi, W., & Wang, L. (2024) · Molecules · doi:10.3390/molecules29122812 · Cited by 63
Impact of Alzheimer’s Disease on Caregivers in the United States
Vu, M., Mangal, R., Stead, T., Carlos Lopez-Ortiz, C., & Ganti, L. (2022) · Health Psychology Research · doi:10.52965/001c.37454 · Cited by 62 · cited 1×
“The emotional toll is high, causing worry, despair, and exhaustion in those who provide care [35,36].”
BackgroundMemantine Derivatives as Multitarget Agents in Alzheimer’s Disease
Marotta, G., Basagni, F., Rosini, M., & Minarini, A. (2020) · Molecules · doi:10.3390/molecules25174005 · Cited by 61 · cited 2×
“The neurotoxicity seen in AD patients is caused by the glutaminergic system being overactivated, which is inhibited by memantine (labeled as 4 , Figure 5), an NMDAR low-affinity uncompetitive antagonist [37,122–124].”
BackgroundZhu, R.-Z., Chen, M.-Q., Zhang, Z.-W., Wu, T.-Y., & Zhao, W.-H. (2021) · Nutrition · doi:10.1016/j.nut.2021.111355 · Cited by 61 · cited 1×
“Conversely, maintaining cardiovascular health, eating a balanced diet rich in antioxidants, and exercising frequently can all lower the incidence of AD [55,58].”
BackgroundDietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites
Frausto, D. M., Forsyth, C. B., Keshavarzian, A., & Voigt, R. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.736814 · Cited by 61 · cited 1×
“Conversely, maintaining cardiovascular health, eating a balanced diet rich in antioxidants, and exercising frequently can all lower the incidence of AD [55,58].”
BackgroundTau-targeting therapy in Alzheimer’s disease: Critical advances and future opportunities
Guo, Y., Li, S., Zeng, L.-H., & Tan, J. (2022) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2022.16 · Cited by 61
Alzheimer’s Disease: Advances in Drug Development
Piton, M., Hirtz, C., Desmetz, C., Milhau, J., Lajoix, A. D., Bennys, K., Lehmann, S., & Gabelle, A. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180145 · Cited by 60 · cited 4×
“In order to decrease the synthesis of amyloid beta, β - secretase inhibitors (BACE inhibitors) such lanabecestat (labeled as 8 , Figure 5) [157,161,162], verubecestat (labeled as 9 , Figure 5) [157,163,164], and atabecestat (labeled as 10 , Figure 5) target the enzyme Bace-1 [157,165].”
BackgroundInfluentialThe Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer’s Disease
Wiatrak, B., Balon, K., Jawień, P., Bednarz, D., Jęśkowiak, I., & Szeląg, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094862 · Cited by 58 · cited 1×
“Such inflammation may enable inflammatory mediators to cross the blood–brain barrier (BBB) and affect microglia, exacerbating neuroinflammation, which ultimately contributes to neuronal degeneration and damage [17,18].”
BackgroundPredicting early Alzheimer’s with blood biomarkers and clinical features
AlMansoori, M. E., Jemimah, S., Abuhantash, F., & AlShehhi, A. (2024) · Scientific Reports · doi:10.1038/s41598-024-56489-1 · Cited by 58 · cited 2×
“AI systems have been approved by the US Food and Drug Administration (FDA) for enhancing medical imaging assessments, including the identification of suspicious lesions [37,213,216].”
BackgroundThe Implications of Autophagy in Alzheimer’s Disease
Hamano, T., Hayashi, K., Shirafuji, N., & Nakamoto, Y. (2018) · Current Alzheimer Research · doi:10.2174/1567205015666181004143432 · Cited by 57 · cited 1×
“These defects may arise from genetic factors, reduced expression of related proteins, and impaired vesicular transportation, ultimately resulting in the accumulation of damaged organelles, such as dysfunctional mitochondria [22,23].”
BackgroundZhu, Z., & Reiser, G. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.02.006 · Cited by 56 · cited 1×
“Molecular chaperones can be classified as either external (clustered proteins, such alpha-macroglobulin and clustering) or intracellular (heat shock proteins, such as Hsp40, Hsp60, Hsp70, Hsp90, Hsp100, and Hsp110) [37,99,100].”
BackgroundPocock, J., Vasilopoulou, F., Svensson, E., & Cosker, K. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110020 · Cited by 54
Hu, J., Pan, T., An, B., Li, Z., Li, X., & Huang, L. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.12.013 · Cited by 53
Morató, X., Pytel, V., Jofresa, S., Ruiz, A., & Boada, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169305 · Cited by 53 · cited 3×
“DMTs are intended to delay the progression of long-term conditions such as AD and ultimately improve the patient’s quality of life [60].”
BackgroundWiels, W. A., Wittens, M. M. J., Zeeuws, D., Baeken, C., & Engelborghs, S. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.707580 · Cited by 52
Alzheimer's disease diagnosis and management: Perspectives from around the world
Kerwin, D. R., Ruiz, C. A., Caramelli, P., Ogunniyi, A. O., Shi, J., Zetterberg, H., & Traber, M. (2022) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12334 · Cited by 51 · cited 1×
“The emotional toll is high, causing worry, despair, and exhaustion in those who provide care [35,36].”
BackgroundSocial isolation is linked to classical risk factors of Alzheimer’s disease-related dementias
Shafighi, K., Villeneuve, S., Rosa Neto, P., Badhwar, A., Poirier, J., Sharma, V., Medina, Y. I., Silveira, P. P., Dube, L., Glahn, D., et al. (2023) · PLOS ONE · doi:10.1371/journal.pone.0280471 · Cited by 51 · cited 1×
“AD risk factors include obesity, diabetes, high blood pressure, and high cholesterol [51–53].”
BackgroundGentreau, M., Chuy, V., Féart, C., Samieri, C., Ritchie, K., Raymond, M., Berticat, C., & Artero, S. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12114 · Cited by 50 · cited 1×
“Furthermore, sedentary lifestyles and bad dietary habits, such as consuming large amounts of carbs and saturated fats, have been connected to an increased risk [54–57].”
BackgroundThe role of TREM2 in Alzheimer’s disease: from the perspective of Tau
Huang, W., Huang, J., Huang, N., & Luo, Y. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1280257 · Cited by 49
The Role of Amyloid-Beta and Tau in the Early Pathogenesis of Alzheimer’s Disease
Yin, X., Qiu, Y., Zhao, C., Zhou, Z., Bao, J., & Qian, W. (2021) · Medical Science Monitor · doi:10.12659/msm.933084 · Cited by 48 · cited 1×
“Based on how they work, DMTs can be divided into a number of categories [37,76,83].”
BackgroundThe role of genetic risk factors of Alzheimer’s disease in synaptic dysfunction
Fu, W.-Y., & Ip, N. Y. (2023) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2022.07.011 · Cited by 48
Behl, T., Kaur, I., Frățilă, O., Brata, R. D., & BUNGAU, S. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207443 · Cited by 47 · cited 1×
“This entails protecting neurons from oxidative stress and inflammation, among other potential causes of injury [73–75].”
BackgroundVicente-Zurdo, D., Rosales-Conrado, N., León-González, M. E., Brunetti, L., Piemontese, L., Pereira-Santos, A. R., Cardoso, S. M., Madrid, Y., Chaves, S., & Santos, M. A. (2022) · Biomedicines · doi:10.3390/biomedicines10071510 · Cited by 47
Yaghmaei, E., Lu, H., Ehwerhemuepha, L., Zheng, J., Danioko, S., Rezaie, A., Sajjadi, S. A., & Rakovski, C. (2024) · Communications Medicine · doi:10.1038/s43856-024-00527-6 · Cited by 47 · cited 2×
“Constipation, headache, nausea, vomiting, lack of appetite, increased frequency of bowel movements, dizziness, disorientation, and headaches are among the side effects [127–129].”
BackgroundNdebele, P., Blanchard-Horan, C., Shahkolahi, A., & Sanne, I. (2014) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000000037 · Cited by 46 · cited 1×
“Moreover, biobanking and repository research are being scrutinized and restricted more harshly [196,197].”
BackgroundNew Possibilities in the Therapeutic Approach to Alzheimer’s Disease
Doroszkiewicz, J., & Mroczko, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23168902 · Cited by 46
Monoclonal Antibody Therapy in Alzheimer’s Disease
Neațu, M., Covaliu, A., Ioniță, I., Jugurt, A., Davidescu, E. I., & Popescu, B. O. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics16010060 · Cited by 46 · cited 2×
“Clinical trials have investigated many anti-A β antibodies, such as solanezumab [145,146], bapineuzumab [147–149], and aducanuamb.”
BackgroundTargeting dementias through cancer kinases inhibition
Fagiani, F., Lanni, C., Racchi, M., & Govoni, S. (2020) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12044 · Cited by 43 · cited 1×
“The tyrosine kinase inhibitor saracatinib (AZD0530 (labeled as 14 , Figure 5)) is undergoing Phase II trials [174–176] and has been demonstrated to improve memory in transgenic mice models of AD.”
BackgroundAlzheimer’s disease research: The future of BACE inhibitors
Burki, T. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31425-9 · Cited by 40 · cited 1×
“In order to decrease the synthesis of amyloid beta, β - secretase inhibitors (BACE inhibitors) such lanabecestat (labeled as 8 , Figure 5) [157,161,162], verubecestat (labeled as 9 , Figure 5) [157,163,164], and atabecestat (labeled as 10 , Figure 5) target the enzyme Bace-1 [157,165].”
BackgroundMachauer, R., Lueoend, R., Hurth, K., Veenstra, S. J., Rueeger, H., Voegtle, M., Tintelnot-Blomley, M., Rondeau, J.-M., Jacobson, L. H., Laue, G., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01300 · Cited by 40 · cited 1×
“Similar to other BACE-1 inhibitors, CNP520 (umibeces-tat (labeled as 11 , Figure 5)) has been shown to reduce the burden of amyloid-beta plaques in preclinical animals; it is presently undergoing testing phases [157,166,167].”
BackgroundGuo, Q., Li, Y., Xu, S., Wang, P., Qian, K., Yang, P., Sheng, D., Wang, L., Cheng, Y., Meng, R., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.01.074 · Cited by 40 · cited 1×
“In order to preserve microtubules and maintain neuronal function, neuroprotective agents—substances such as NAP, the activity-dependent neuroprotective protein generated from ADNP—have been shown to be useful in preventing the death of neurons [211,212].”
BackgroundHeavy Metals and Neurological Disorders: From Exposure to Preventive Interventions
Rehman, Q., Rehman, K., & Akash, M. S. H. (2021) · Emerging Contaminants and Associated Treatment Technologies · doi:10.1007/978-3-030-66376-6_4 · Cited by 39 · cited 1×
“Dementia risk has been shown to rise with toxic exposure to heavy metals as lead, mercury, and aluminum [45–48].”
BackgroundYang, J. J., Keohane, L. M., Pan, X.-F., Qu, R., Shu, X.-O., Lipworth, L., Braun, K., Steinwandel, M. D., Dai, Q., Shrubsole, M., et al. (2022) · Neurology · doi:10.1212/wnl.0000000000200774 · Cited by 39 · cited 2×
“AD risk factors include obesity, diabetes, high blood pressure, and high cholesterol [51–53].”
BackgroundJurcău, A., & Simion, A. (2020) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527319666200303121016 · Cited by 38 · cited 1×
“Additionally, the presence of free metals and complexes of A β can catalyze ROS production, further exacerbating neuronal damage [19,20].”
BackgroundLiew, T. M. (2021) · Age and Ageing · doi:10.1093/ageing/afab044 · Cited by 38 · cited 2×
“Those who have the condition also exhibit neuropsychiatric symptoms, and with time, they lose their ability to perform basic daily duties [24–28].”
BackgroundQiao, Y., Gu, J., Yu, M., Chi, Y., & Ma, Y. (2024) · CNS Drugs · doi:10.1007/s40263-024-01067-2 · Cited by 38 · cited 3×
“Aducanumab in particular was more likely to cause ARIA-E (edema) [37,92].”
BackgroundSaeedi, M., & Mehranfar, F. (2022) · Recent Patents on Biotechnology · doi:10.2174/1872208316666220302115901 · Cited by 36 · cited 1×
“AChE and BuChE metabolize it at the synapse [115,116].”
BackgroundAttademo, L., & Bernardini, F. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200289 · Cited by 35 · cited 1×
“Moreover, exposure to air pollution may worsen neuroinflammation and cognitive decline [49,50].”
BackgroundPossible Consequences of the Approval of a Disease-Modifying Therapy for Alzheimer Disease
Musiek, E. S., & Morris, J. C. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.4478 · Cited by 35
Adesuyan, M., Jani, Y. H., Alsugeir, D. M., Howard, R. J., Ju, C., Wei, L., & Brauer, R. (2024) · Neurology · doi:10.1212/wnl.0000000000209131 · Cited by 35 · cited 1×
“Scientists are beginning to investigate whether they could be helpful for neurological illnesses, even though they have primarily been studied for conditions including asthma and chronic obstructive pulmonary disease (COPD) [181].”
BackgroundHe, F., Tang, J., Zhang, T., Lin, J., Li, F., Gu, X., Chen, A., Nevill, A., & Chen, R. (2022) · Environmental Research · doi:10.1016/j.envres.2021.112318 · Cited by 34 · cited 1×
“Moreover, exposure to air pollution may worsen neuroinflammation and cognitive decline [49,50].”
BackgroundWessels, A. M., Dennehy, E. B., Dowsett, S. A., Dickson, S. P., & Hendrix, S. B. (2023) · Neurology Clinical Practice · doi:10.1212/cpj.0000000000200127 · Cited by 34 · cited 1×
“These therapies aim to preserve neuronal connectivity and function by concentrating on specific pathological pathways [69–71].”
BackgroundAlzheimer’s disease: From basic science to precision medicine approach
Forloni, G. (2020) · BMJ Neurology Open · doi:10.1136/bmjno-2020-000079 · Cited by 33 · cited 1×
“AI systems have been approved by the US Food and Drug Administration (FDA) for enhancing medical imaging assessments, including the identification of suspicious lesions [37,213,216].”
BackgroundDiscontinued disease-modifying therapies for Alzheimer’s disease: status and future perspectives
Imbimbo, B. P., Lozupone, M., Watling, M., & Panza, F. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1795127 · Cited by 31 · cited 2×
“While symptomatic therapies may provide immediate relief from pain or fatigue, DMTs specifically work to change the immune response or repair brain damage [64,65].”
BackgroundGuo, H., Wang, G., Zhai, Z., Huang, J., Huang, Z., Zhou, Y., Xia, X., Yao, Z., Huang, Y., Zhao, Z., et al. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.123809 · Cited by 31
Personalizing the Care and Treatment of Alzheimer’s Disease: An Overview
Štrac, D. Š., Konjevod, M., Šagud, M., Perković, M. N., Erjavec, G. N., Vuić, B., Šimić, G., Vukić, V., Mimica, N., & Pivac, N. (2021) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s284615 · Cited by 30 · cited 1×
“This approach is adaptable enough to be customized for every single patient, ensuring optimal treatment outcomes [220,221].”
BackgroundCurrent therapeutics for Alzheimer’s disease and clinical trials
Xiao, D., & Zhang, C. (2024) · Exploration of Neuroscience · doi:10.37349/en.2024.00048 · Cited by 30
Rajkumar, M., Sakthivel, M., Senthilkumar, K., Thangaraj, R., & Kannan, S. (2022) · Current Research in Pharmacology and Drug Discovery · doi:10.1016/j.crphar.2022.100100 · Cited by 29 · cited 2×
“It is a first-line medication for mild-to-severe AD that has a good efficacy and tolerability in improving behavioral symptoms, activities of daily living, and cognitive performance [110,112,113].”
BackgroundSantos, G. S., Sinoti, S. B. P., de Almeida, F. T. C., Silveira, D., Simeoni, L. A., & Gomes-Copeland, K. K. P. (2020) · Plant Cell Tissue and Organ Culture (PCTOC) · doi:10.1007/s11240-020-01911-5 · Cited by 28 · cited 1×
“It is a first-line medication for mild-to-severe AD that has a good efficacy and tolerability in improving behavioral symptoms, activities of daily living, and cognitive performance [110,112,113].”
BackgroundDong, Y., Lu, J., Zhang, S., Chen, L., Wen, J., Wang, F., Mao, Y., Li, L., Zhang, J., Liao, S., et al. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106446 · Cited by 28 · cited 1×
“Tideglusib (NP-031112 (labeled as 13 , Figure 5)), an inhibitor of GSK3 β , targets tau hyperphosphorylation, which is required for the development of tau tangles [171–173].”
BackgroundRiviere, M., Langbaum, J. B., Turner, R. S., Rinne, J. O., Sui, Y., Cazorla, P., Ricart, J., Meneses, K., Caputo, A., Tariot, P. N., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13532 · Cited by 28 · cited 1×
“It involves administering multiple doses of the whole A β 1–6 peptide linked to the ADP-Q carrier, a virus-like particle that generates high-titer anti-A β antibodies [140,141,153,154].”
BackgroundLanabecestat: Neuroimaging results in early symptomatic Alzheimer’s disease
Zimmer, J. A., Shcherbinin, S., Devous, M. D., Bragg, S. M., Selzler, K. J., Wessels, A. M., Shering, C., Mullen, J., Landry, J., Andersen, S. W., et al. (2021) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12123 · Cited by 27 · cited 1×
“In order to decrease the synthesis of amyloid beta, β - secretase inhibitors (BACE inhibitors) such lanabecestat (labeled as 8 , Figure 5) [157,161,162], verubecestat (labeled as 9 , Figure 5) [157,163,164], and atabecestat (labeled as 10 , Figure 5) target the enzyme Bace-1 [157,165].”
BackgroundVersatile nanomaterials for Alzheimer’s disease: Pathogenesis inspired disease-modifying therapy
Xi, Y., Chen, Y., Jin, Y., Han, G., Song, M., Song, T., Shi, Y., Tao, L., Huang, Z., Zhou, J., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.02.034 · Cited by 27
Turcu, A. L., Companys-Alemany, J., Phillips, M. B., Patel, D. S., Griñán-Ferré, C., Loza, M. I., Brea, J. M., Pérez, B., Soto, D., Sureda, F. X., et al. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114354 · Cited by 27
Exploring the effects of methylene blue on amyloid fibrillogenesis of lysozyme
How, S.-C., Cheng, Y.-H., Lo, C.-H., Lai, J.-T., Lin, T.-H., Bednarikova, Z., Antosova, A., Gazova, Z., Wu, J. W., & Wang, S. S.-S. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.08.038 · Cited by 25 · cited 1×
“Due to problems with binding efficiency, which show up as blue discolorations in urine, methylene blue (labeled as 12 , Figure 5), which was also tried in Phase II clinical trials for mild-to-moderate AD (for suppressing tau aggregation), has drawn a lot of criticism [168–170].”
BackgroundMolecular mechanisms of altered adult hippocampal neurogenesis in Alzheimer's disease
Liu, H., Zhang, H., & Ma, Y. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111452 · Cited by 25 · cited 1×
“Moreover, DMTs work to prolong patients’ independence as much as possible in order to enhance their general quality of life [79–81].”
BackgroundTherapeutic Strategies Aimed at Improving Neuroplasticity in Alzheimer Disease
Colavitta, M. F., & Barrantes, F. J. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15082052 · Cited by 25 · cited 1×
“Moreover, DMTs work to prolong patients’ independence as much as possible in order to enhance their general quality of life [79–81].”
BackgroundRoflumilast: A potential drug for the treatment of cognitive impairment?
Sugin, L. J. S., Murugesan, A., Bindu, M., & Sunil, K. N. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135281 · Cited by 24
Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer’s disease
Wu, L., Zhou, X., Cao, Y., MAK, S. H., Zha, L., Li, N., Su, Z., Han, Y., Wang, Y., Man Hoi, M. P., et al. (2021) · Aging Cell · doi:10.1111/acel.13371 · Cited by 24 · cited 1×
“Memantine is safe and well-tolerated; it is used to treat moderate-to-severe AD alone or in combination with AChEI [124–126].”
BackgroundCurrent peptide vaccine and immunotherapy approaches against Alzheimer’s disease
Parrocha, C. M. T., & Nowick, J. S. (2023) · Peptide Science · doi:10.1002/pep2.24289 · Cited by 24 · cited 1×
“It involves administering multiple doses of the whole A β 1–6 peptide linked to the ADP-Q carrier, a virus-like particle that generates high-titer anti-A β antibodies [140,141,153,154].”
BackgroundRibba, B. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1094281 · Cited by 24 · cited 1×
“The indicated BBB penetration values are inconsistent with the physicochemical characteristics of monoclonal antibodies (solanezumab, aducanumab, bapineuzumab) or gamma-secretase inhibitors (semagacestat, tarenflurbil) [193–195].”
Dual Drug Repurposing: The Example of Saracatinib
Ramos, R., & Vale, N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084565 · Cited by 24
Ekundayo, T. C., Olasehinde, T. A., Okaiyeto, K., & Okoh, A. I. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.648484 · Cited by 23 · cited 1×
“For this reason, there are still problems associated with this illness that scientists and physicians encounter globally [3,4].”
BackgroundFerreira, A. C. F., Szeto, A. C. H., Clark, P. A., Crisp, A., Kozik, P., Jolin, H. E., & McKenzie, A. N. J. (2023) · Immunity · doi:10.1016/j.immuni.2023.05.010 · Cited by 23 · cited 1×
“In order to preserve microtubules and maintain neuronal function, neuroprotective agents—substances such as NAP, the activity-dependent neuroprotective protein generated from ADNP—have been shown to be useful in preventing the death of neurons [211,212].”
BackgroundAlzheimer’s Disease: Dawn of a New Era?
Amirrad, F., Bousoik, E., Shamloo, K., Al-Shiyab, H., Nguyen, V.-H. V., & Montazeri Aliabadi, H. (2017) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/j3vs8p · Cited by 21 · cited 1×
“These tables represent agents in the three phases of disease-modifying agents’ development for AD [38,46,68,70,71,157,182,183,189].”
BackgroundConrado, D. J., Duvvuri, S., Geerts, H., Burton, J., Biesdorf, C., Ahamadi, M., Macha, S., Hather, G., Francisco Morales, J., Podichetty, J., et al. (2020) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1782 · Cited by 21 · cited 1×
“The indicated BBB penetration values are inconsistent with the physicochemical characteristics of monoclonal antibodies (solanezumab, aducanumab, bapineuzumab) or gamma-secretase inhibitors (semagacestat, tarenflurbil) [193–195].”
Novel approaches to increase synaptic resilience as potential treatments for Alzheimer’s disease
Pham, A. Q., & Dore, K. (2023) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2022.03.032 · Cited by 21 · cited 1×
“Examples of medications that may improve synaptic function include those that allosterically increase the M1 muscarinic acetylcholine receptor [209,210].”
BackgroundDevelopment of new Alzheimer’s disease drug candidates using donepezil as a key model
Eissa, K. I., Kamel, M. M., Mohamed, L. W., & Kassab, A. E. (2023) · Archiv der Pharmazie · doi:10.1002/ardp.202200398 · Cited by 20 · cited 1×
“By re-versibly binding to acetylcholinesterase, it slows the hydrolysis of acetylcholine, increasing the concentration of ACh at synapses [106,107].”
BackgroundFDA approves second anti-amyloid antibody for Alzheimer disease
Mullard, A. (2023) · Nature Reviews Drug Discovery · doi:10.1038/d41573-023-00004-0 · Cited by 19
Holdridge, K. C., Yaari, R., Hoban, D. B., Andersen, S., & Sims, J. R. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13031 · Cited by 19 · cited 1×
“However, AN-1792 was withdrawn during Phase II of the trial due to side effects associated with meningoencephalitis, which were reported in 6% of patients [140–144].”
BackgroundTherapeutic and medicinal effects of snowdrop (Galanthus spp.) in Alzheimer's disease: A review
Babashpour-Asl, M., Kaboudi, P. S., & Barez, S. R. (2023) · Journal of Education and Health Promotion · doi:10.4103/jehp.jehp_451_22 · Cited by 19 · cited 1×
“With a dual mode of action, galantamine (labeled as 2 , Figure 5) is a selective tertiary isoquinoline alkaloid that may both bind allosterically to the α -subunit of nicotinic acetylcholine receptors and activate them, as well as competitively inhibit AChE [110,111].”
BackgroundHeneghan, A., Deng, F., Wells, K., Ritchie, K., Muniz-Terrera, G., Ritchie, C. W., Lawlor, B., & Naci, L. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-220267 · Cited by 18
Methylene Blue Blocks and Reverses the Inhibitory Effect of Tau on PMCA Function
Berrocal, M., Caballero-Bermejo, M., Gutierrez-Merino, C., & Mata, A. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143521 · Cited by 17
Molecular mechanisms of Alzheimer’s disease: From therapeutic targets to promising drugs
Alan, E., Kerry, Z., & Sevin, G. (2023) · Fundamental & Clinical Pharmacology · doi:10.1111/fcp.12861 · Cited by 17 · cited 1×
“This includes γ -secretase inhibitors, such as tarenflurbil ( 7 , Figure 5) [155,156], avagacestat (labeled as 6 , Figure 5) [157,158], and semagacestat ( 5 , Figure 5) [159,160].”
BackgroundParums, D. V. (2021) · PubMed Central · doi:10.12659/msm.934077 · Cited by 17
A review of neuroimaging-based data-driven approach for Alzheimer’s disease heterogeneity analysis
Liu, L., Sun, S., Kang, W., Wu, S., & Lin, L. (2024) · Reviews in the Neurosciences · doi:10.1515/revneuro-2023-0033 · Cited by 16
Immunotherapeutic approaches for Alzheimer’s disease: Exploring active and passive vaccine progress
Bhadane, P., Roul, K., Belemkar, S., & Kumar, D. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149018 · Cited by 15 · cited 2×
“It involves administering multiple doses of the whole A β 1–6 peptide linked to the ADP-Q carrier, a virus-like particle that generates high-titer anti-A β antibodies [140,141,153,154].”
BackgroundTherapeutic news in Alzheimer’s disease: Soon a disease-modifying therapy?
Villain, N. (2022) · Revue Neurologique · doi:10.1016/j.neurol.2022.02.456 · Cited by 14 · cited 1×
“This shift in focus is crucial for treating progressive illnesses because it addresses both the disease’s symptoms and the underlying issues that cause it to worsen [61,65–67].”
BackgroundNiidome, T., Ishikawa, Y., Ogawa, T., Nakagawa, M., & Nakamura, Y. (2024) · Folia Pharmacologica Japonica · doi:10.1254/fpj.24005 · Cited by 14
A Chronological Review of Potential Disease-Modifying Therapeutic Strategies for Alzheimer’s Disease
Ettcheto, M., Busquets, O., Espinosa-Jiménez, T., Verdaguer, E., Auladell, C., & Camins, A. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200211121416 · Cited by 13 · cited 1×
“This includes γ -secretase inhibitors, such as tarenflurbil ( 7 , Figure 5) [155,156], avagacestat (labeled as 6 , Figure 5) [157,158], and semagacestat ( 5 , Figure 5) [159,160].”
BackgroundKaur, J., Melkani, I., Singh, A. P., Singh, A. P., & Bala, K. (2022) · Journal of Drug Delivery and Therapeutics · doi:10.22270/jddt.v12i4.5426 · Cited by 13 · cited 1×
“It is a first-line medication for mild-to-severe AD that has a good efficacy and tolerability in improving behavioral symptoms, activities of daily living, and cognitive performance [110,112,113].”
BackgroundHao, Y., Dong, M., Sun, Y., Duan, X., & Niu, W. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1147757 · Cited by 13
Abbate, C., Trimarchi, P. D., Inglese, S., Tomasini, E., Bagarolo, R., Giunco, F., & Cesari, M. (2021) · Applied Neuropsychology Adult · doi:10.1080/23279095.2019.1630626 · Cited by 10 · cited 2×
“Those who have the condition also exhibit neuropsychiatric symptoms, and with time, they lose their ability to perform basic daily duties [24–28].”
Background
Research works printed but not linked: 1
- Horani, 2015, Anticancer Prodrugs—Three Decades of Design, World J. Pharm. Pharm. Sci., 4, 1751
Cited by
Sorted by citations
Antibacterial Activity and Antifungal Activity of Monomeric Alkaloids
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, R., Scrano, L., & Bufo, S. A. (2024) · Toxins · doi:10.3390/toxins16110489 · Cited by 61
Self-citationAlkhalifa, A. E., Mokhlf, A. A., Ali, H., Al-Ghraiybah, N. F., & Syropoulou, V. (2025) · Journal of Personalized Medicine · doi:10.3390/jpm15090437 · Cited by 68
“Adu-canumab was the first anti-amyloid antibody to receive regulatory approval for mild AD with confirmed amyloid pathology, followed by lecanemab and donanemab [21].”
NLRP3 inflammasome in Alzheimer’s disease: molecular mechanisms and emerging therapies
Li, Z., & Gong, C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1583886 · Cited by 53
“The ongoing phase 3 trial TRAILBLAZER-ALZ 2 (NCT04437511) (118), phase 2 clinical trial (NCT04795466) (81) and other AD clinical trials will offer a more comprehensive strategy for AD treatment (119) (Table 1).”
ALNasser, M. N., Alboraiy, G. M., Alsowig, E. M., & Alqattan, F. M. (2025) · Brain Sciences · doi:10.3390/brainsci15020215 · Cited by 35
Targeting of PP2 A/GSK3β/PTEN Axis in Alzheimer Disease: The Mooting Evidence, Divine, and Devil
Alqahtani, S. M., Al-Kuraishy, H. M., Al-Gareeb, A. I., Abdel‐Fattah, M. M., Alsaiari, A. A., Alruwaili, M., Papadakis, M., Alexiou, A. T., & Batiha, G. E. (2025) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-025-01554-0 · Cited by 26
“Similar to other BACE‑1 inhibitors, umibecestat has been shown to reduce the burden of Aβ in preclinical animals (Weaver 2023; Thawabteh et al. 2024).”
Metadata
- Authors
- Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R.
- Affiliations
- Birzeit University (PS)
- Al-Quds University (PS)
- University of Basilicata (IT)
- Corresponding author
- Karaman, Rafik
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2024-10-30
- Volume
- 29
- Issue
- 21
- Pages
- 5131
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC11547905
- OpenAlex
- W4403924413
- Semantic Scholar
- 3b5aac7de909b8d17998af8b07fc6969ccab0114
- Cited by
- 56
- References
- 227
- Citations by year
- 2026: 24 · 2025: 30 · 2024: 2
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, disease-modifying therapy, amyloid-beta, tau protein, neuroinflammation, anti-amyloid therapy, neuroprotective therapy, neurogenesis, cognitive decline, FDA-approved drugs, clinical trials, small molecule drugs, biologics
- MeSH terms
- Alzheimer Disease, Animals, Clinical Trials as Topic, Humans, Amyloid beta-Peptides, tau Proteins, Neuroprotective Agents
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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