The DOI matches its Crossref record; 85 of the 86 references it cites were found in a registry or an index; none of the 50 sources its claims cite is checked for support yet.
Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update
Open accessAbstract
Alzheimer's disease (AD) is the leading cause of dementia, presenting a significant unmet medical need worldwide. The pathogenesis of AD involves various pathophysiological events, including the accumulation of amyloid and tau, neuro-inflammation, and neuronal injury. Clinical trials focusing on new drugs for AD were documented in 2020, but subsequent developments have emerged since then. Notably, the US-FDA has approved Aducanumab and Lecanemab, both antibodies targeting amyloid, marking the end of a nearly two-decade period without new AD drugs. In this comprehensive report, we review all trials listed in clinicaltrials.gov, elucidating their underlying mechanisms and study designs. Ongoing clinical trials are investigating numerous promising new drugs for AD. The main trends in these trials involve pathophysiology-based, disease-modifying therapies and the recruitment of participants in earlier stages of the disease. These trends underscore the significance of conducting fundamental research on pathophysiology, prevention, and intervention prior to the occurrence of brain damage caused by AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This 2020–2023 update reviews Alzheimer disease drug trials listed on ClinicalTrials.gov and highlights the FDA approvals of aducanumab and lecanemab. It finds that trials increasingly focus on disease-modifying anti-amyloid/anti-tau therapies and earlier disease stages, while symptomatic, anti-neuroinflammation, and other approaches remain active.
Key findings
- The FDA granted accelerated approval to aducanumab in June 2021, accelerated approval to lecanemab on January 6, 2023, and traditional approval to lecanemab on July 6, 2023; donanemab had an application for full approval.
- In the lecanemab Clarity AD trial, CDR-SB difference was −0.45 (95% CI −0.67 to −0.23), amyloid PET burden difference was −59.1 (95% CI −62.6 to −55.6), ADAS-Cog14 mean difference was −1.44 (95% CI −2.27 to −0.61), ADCOMS mean difference was −0.050 (95% CI −0.074 to −0.027), and ADCS-MCI-ADL mean difference was 2.0 (95% CI 1.2 to 2.8); ARIA-E occurred in 12.6% and infusion-related reactions in 26.4%.
- In TRAILBLAZER-ALZ 2, donanemab produced iADRS change of −6.02 vs −9.27 for placebo in the low/medium tau group and −10.2 vs −13.1 in the combined population, with a reported 60% reduction in decline in early-stage AD; ARIA occurred in 24% vs 2.1% and infusion-related reactions in 8.7% vs 0.5%. In TRAILBLAZER-ALZ 4, 38% of donanemab-treated patients vs 2% of aducanumab-treated patients were below the amyloid positivity threshold at 6 months, plasma pTau217 decreased by 25% with donanemab but not with aducanumab, and ARIA-edema occurred in 22% of both groups.
- The review reports that most trials continue to target amyloid and tau, with a shift toward prodromal/preclinical populations; BIIB080 produced dose-dependent 30%–50% reductions in CSF total tau and pTau181. Among trials newly registered in the last 4 years, four articles from two trials were published, and both trials had overall low risk of bias.
Methods
- Narrative review/update of Alzheimer disease clinical trials listed on ClinicalTrials.gov, covering 2020–2023, with tables summarizing ongoing phase 2, phase 3, and phase 4 trials by mechanism.
- The paper describes trial agents, targets, designs, outcomes, and status; for published results, it identified four articles pertaining to two trials newly registered in the last 4 years and assessed methodological quality using the Cochrane risk of bias tool, version 2.
- No systematic search, meta-analysis, or pooled effect estimate is described.
Limitations
- The paper does not state a formal limitations section. Evident from the text: it is a descriptive review relying on ClinicalTrials.gov listings and selected published results, without a systematic search or quantitative synthesis.
- Many cited trials are ongoing or not yet recruiting, so efficacy and safety results are unavailable; the review notes challenges including limited indications for anti-amyloid monoclonal antibodies, administration and monitoring costs, need for specialized facilities and imaging, and unmet needs for BPSD and cognitive enhancement.
- Risk-of-bias assessment was limited to four published articles from two trials; other trial data were not quality-assessed.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
42 Not checked yet · 13 No basis given · 9 Own interpretation · 8 Own result · 4 Own method
In the paper
“A double-blind, placebo-controlled phase 2 trial recruited 856 patients with AD with mild cognitive impairment (MCI) or mild dementia and verified amyloid pathology through amyloid PET or CSF Aβ1-42 [42].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [42] Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RY, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13(1):80. source
plainn = 856- 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 preliminary results were presented at the 2022 Clinical Trial of AD (CTAD) conference: 38% of the patients on donanemab exhibited amyloid levels below the amyloid positivity threshold after 6 months, whereas only 2% of the patients on aducanumab has such findings.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
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.
In the paper
“It reported favorable outcomes for all primary and secondary measures, including ADAS-Cog14, AD Composite Score (ADCOMS), and ADCS-MCI-ADL scores [43].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [43] Van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21. 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.
In the paper
“An exploratory analysis revealed that a subgroup of the participants in the ENGAGE trial who received a high dose of aducanumab exhibited slow decline, which was similar to that observed among the participants in the EMERGE trial.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [39] Dunn B, Stein P, Cavazzoni P. Approval of aducanumab for Alzheimer disease—the FDA’s perspective. JAMA Intern Med. 2021;181(10):1276–8. 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.
In the paper
“On July 6, 2023, Leqembi (lecanemab-irmb) received traditional approval from the US FDA for the treatment of AD based on Phase 3 data from the Clarity AD clinical trial [17].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [17] FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval-Action Follows Confirmatory Trial to Verify Clinical Benefit. 2023.
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.
In the paper
“Adverse effects included amyloid-related imaging problems (24% donanemab vs. 2.1% placebo) and infusion-related reactions (8.7% donanemab vs. 0.5% placebo).”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [50] Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512–27. source
plaindirectn = 1,736- 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.
In the paper
“The results revealed a significant and dose-dependent reduction of amyloid plaques in the lecanemab group (10 mg/kg, intravenous infusion every 2 weeks) from baseline to week 79 compared with the placebo group.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [42] Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RY, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13(1):80. source
plaindirectn = 856- 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.
In the paper
“However, the findings of the EMERGE trial reached statistical significance, whereas the primary endpoint was not reached in the ENGAGE trial.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [39] Dunn B, Stein P, Cavazzoni P. Approval of aducanumab for Alzheimer disease—the FDA’s perspective. JAMA Intern Med. 2021;181(10):1276–8. 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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The US FDA approved aducanumab in June 2021 on the basis of the data of the EMERGE and ENGAGE trials.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
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.
In the paper
“Donanemab reduced the tau burden in the temporal, parietal, and frontal lobes and significantly decreased plasma pTau217 by 24% in the treatment group, whereas the placebo group exhibited a 6% increase in plasma pTau217 at the end of the trial [49].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [49] Pontecorvo MJ, Lu M, Burnham SC, Schade AE, Dage JL, Shcherbinin S, et al. Association of donanemab treatment with exploratory plasma biomarkers in early symptomatic Alzheimer disease: a secondary analysis of the TRAILBLAZER-ALZ randomized clinical trial. JAMA Neurol. 2022;79(12):1250–9. 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.
- Probably not a substantial claim. 13
- It may state two separate claims as one. 18
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Clinical trials of early or preventive interventions based on amyloid/tau theory and those targeting other pathophysiologies are ongoing or have been initiated.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background
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.
Probably not a substantial claim. It may state two separate claims as one.
- Rests on an assumption: The key event in AD pathogenesis is Aβ accumulation.
In the paper
“Donanemab reduced the tau burden in the temporal, parietal, and frontal lobes and significantly decreased plasma pTau217 by 24% in the treatment group, whereas the placebo group exhibited a 6% increase in plasma pTau217 at the end of the trial [49].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [49] Pontecorvo MJ, Lu M, Burnham SC, Schade AE, Dage JL, Shcherbinin S, et al. Association of donanemab treatment with exploratory plasma biomarkers in early symptomatic Alzheimer disease: a secondary analysis of the TRAILBLAZER-ALZ randomized clinical trial. JAMA Neurol. 2022;79(12):1250–9. 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
“Both trials presented evidence of an intermediate effect of the drug on biomarkers, indicating amyloid removal, which is likely linked to the clinical benefit of aducanumab.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [39] Dunn B, Stein P, Cavazzoni P. Approval of aducanumab for Alzheimer disease—the FDA’s perspective. JAMA Intern Med. 2021;181(10):1276–8. 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.
It may state two separate claims as one.
In the paper
“The US FDA approved it on January 6, 2023, through an accelerated approval pathway on the basis of evidence of amyloid removal in a phase 2 trial (NCT01767311) and because it had a likelihood of having clinical benefits [41]”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [41] Canady VA. FDA approves new treatment for Alzheimer’s disease. Ment Heal Wkly. 2023;33(3):6–7. source
plaindirectn = 856- 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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Plasma pTau217 levels decreased by 25% for the participants receiving donanemab, but not at all for those receiving aducanumab.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Clinical trials related to AD have also exhibited a shift in focus toward the earlier stages of AD, such as MCI, or even cognitively healthy participants for developing prevention interventions.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Discussion
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: 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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This shift in perspective has led to a change in the focus of research toward populations in the prodromal or preclinical stage with positive results for diagnostic biomarkers.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Discussion
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, despite this expansion of research areas, the scope of indications for novel anti-amyloid monoclonal antibody therapy remains limited.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Discussion
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
“Two articles reported the results of NCT03887455 [43, 84], and the other two reported the results of NCT01760005 [53, 83].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Published results
What the sources say
- Not checked yetcites [43] Van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21. source
- Not checked yetcites [84] Tahami Monfared AA, Ye W, Sardesai A, Folse H, Chavan A, Aruffo E, et al. A path to improved Alzheimer’s care: simulating long-term health outcomes of lecanemab in early Alzheimer’s disease from the CLARITY AD trial. Neurol Ther. 2023;12(3):863–81. source
- Not checked yetcites [53] Salloway S, Farlow M, McDade E, Clifford DB, Wang G, Llibre-Guerra JJ, et al. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease. Nat Med. 2021;27(7):1187–96. source
- Not checked yetcites [83] Bateman RJ, Benzinger TL, Berry S, Clifford DB, Duggan C, Fagan AM, et al. The DIAN-TU Next Generation Alzheimer’s prevention trial: Adaptive design and disease progression model. Alzheimers Dement. 2017;13(1):8–19. 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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Overall, the field of AD clinical trials is evolving, and additional promising treatments for AD are likely to be developed in the near future.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Conclusion
plain- 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: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
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
“The articles were published between 2018 and 2023.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Published results
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.
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
“Many ongoing clinical trials on AD are focused on disease-modifying therapies (DMTs) that target the causes and can change the course of AD.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background
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.
Probably not a substantial claim.
- Rests on an assumption: The key event in AD pathogenesis is Aβ accumulation.
In the paper
“It recognizes Aβ (3–42), an aggregated form of Aβ found in amyloid plaques [46].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [46] Irizarry MC, Sims JR, Lowe SL, Nakano M, Hawdon A, Willis BA, et al. O4–08-06: Safety, pharmacokinetics (PK), and florbetapir F-18 positron emission tomography (PET) after multiple dose administration of LY3002813, a β-amyloid plaque-specific antibody, in Alzheimer’s disease. Alzheimers Dement. 2016;12:P352–3. 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.
In the paper
“Acetylcholine (ACh) plays a vital role in memory function, including memory encoding, consolidation, and retrieval processes, and increasing Ach levels by using cholinesterase inhibitors (AChEIs) has become a standard therapy for the symptoms of AD [37].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background
What the sources say
- Not checked yetcites [37] Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008;148(5):379–97. 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.
In the paper
“Acetylcholine (ACh) plays a vital role in memory function, including memory encoding, consolidation, and retrieval processes, and increasing Ach levels by using cholinesterase inhibitors (AChEIs) has become a standard therapy for the symptoms of AD [37].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background
What the sources say
- Not checked yetcites [37] Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008;148(5):379–97. 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.
In the paper
“Aducanumab (brand name: Aduhelm) is a high-affinity, fully human immunoglobulin gamma 1 (IgG1) monoclonal antibody that binds to the N-terminus of Aβ fibrils and blocks amyloid aggregation [38].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [38] Arndt JW, Qian F, Smith BA, Quan C, Kilambi KP, Bush MW, et al. Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β. Sci Rep. 2018;8(1):6412. 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
“Lecanemab (brand name: Leqembi), a humanized IgG1 antibody derived from mAb158, selectively binds to soluble Aβ protofibrils [40].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [40] Tucker S, Möller C, Tegerstedt K, Lord A, Laudon H, Sjödahl J, et al. The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis. 2015;43(2):575–88. 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.
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 other trials involve symptomatic treatments—for example, enhancing cognitive function and relieving BPSD (Fig. 1).”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background
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
“The appropriate use recommendations (AURs) for lecanemab and aducanumab highlight the importance of patient selection, surveillance for adverse events, and clinician preparedness [44, 45].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [44] Cummings J, Rabinovici G, Atri A, Aisen P, Apostolova L, Hendrix S, et al. Aducanumab: appropriate use recommendations update. J Prev Alzheimers Di s. 2022;9(2):221–30.
- Not checked yetcites [45] Cummings J, Apostolova L, Rabinovici G, Atri A, Aisen P, Greenberg S, et al. Lecanemab: appropriate use recommendations. J Prev Alzheimers Dis. 2023;10(3):362–77.
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.
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 approval of this treatment not only affirms the pathophysiological significance of amyloid in AD but also marks a notable advance in clinical approaches to AD treatment, remedying the scarcity of new drugs in the market for nearly two decades.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background
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
“On March 8, 2023, Eli Lilly and Company reported that solanezumab did not slow cognitive decline or clear amyloid plaques in individuals with preclinical AD in the A4 study.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
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
“Overall, the field of AD clinical trials is evolving, and additional promising treatments for AD are likely to be developed in the near future.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Conclusion
hedged- 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: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
None of the sources cited for this claim have been checked yet.
In the paper
“Both trials (NCT03887455 and NCT01760005) had a overall low risk of bias [43, 53, 83, 84].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Published results
What the sources say
- Not checked yetcites [43] Van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21. source
- Not checked yetcites [53] Salloway S, Farlow M, McDade E, Clifford DB, Wang G, Llibre-Guerra JJ, et al. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease. Nat Med. 2021;27(7):1187–96. source
- Not checked yetcites [83] Bateman RJ, Benzinger TL, Berry S, Clifford DB, Duggan C, Fagan AM, et al. The DIAN-TU Next Generation Alzheimer’s prevention trial: Adaptive design and disease progression model. Alzheimers Dement. 2017;13(1):8–19. source
- Not checked yetcites [84] Tahami Monfared AA, Ye W, Sardesai A, Folse H, Chavan A, Aruffo E, et al. A path to improved Alzheimer’s care: simulating long-term health outcomes of lecanemab in early Alzheimer’s disease from the CLARITY AD trial. Neurol Ther. 2023;12(3):863–81. 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.
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
“Outcome measurement tools have also become more diverse, which has enabled meaningful improvements in AD and the efficacy of treatments to be clearly determined in clinical trials.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Conclusion
boosteddirect- 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.
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 participants were offered an open-label extension with high-dose gantenerumab because of its positive effects on imaging and other biomarkers, such as normalized CSF Aβ42, and because it reduced CSF total tau and pTau181 levels.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
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
“whereas gantenerumab significantly reduced amyloid plaques, CSF total tau, and phospho-tau181 and attenuated increases in neurofilament light chain [53].”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-amyloid therapy
What the sources say
- Not checked yetcites [53] Salloway S, Farlow M, McDade E, Clifford DB, Wang G, Llibre-Guerra JJ, et al. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease. Nat Med. 2021;27(7):1187–96. 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.
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
“Recipients of JACI-35.054 also displayed a robust immune response against ePHF and pTau, but without a clear dose–effect relationship.”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-tau therapy
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.
The paper relies on this without support.
The key event in AD pathogenesis is Aβ accumulation.
“The key event in AD pathogenesis is believed to be Aβ accumulation.”
The paper relies on this without support.
Remternetug is a monoclonal antibody that recognizes a pyroglutamated form of Aβ that aggregates into amyloid plaques.
“Remternetug is a monoclonal antibody that recognizes a pyroglutamated form of Aβ that aggregates into amyloid plaques.”
The paper relies on this without support.
The validity of the amyloid hypothesis has been contested.
“Additionally, the validity of the amyloid hypothesis has been contested, resulting in a significant reduction in the number of anti-amyloid phase 3 trials since 2019.”
The paper relies on this without support.
There is an unmet clinical need for therapies for symptoms including cognitive enhancers and agents for relieving BPSD.
“This reflects the unmet clinical need for such therapies (Figs. 2 and 3).”
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 check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing 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).”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [184]
Experimental — accuracy not yet measuredIn the citing paper
“Phase III trials, including 48 trials that tested 32 medications [37,183,184].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [184]
In the citing paper
“Phase II trials (90 studies, 81 medicines): these trials continue to investigate the drugs’ safety and efficacy.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [184]
In the citing 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].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [184]
In the citing paper
“In Phase I, there are 26 trials assessing 25 agents.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [184]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-tau therapy
“| ACI-35 | AC Immune SA | Tau Morphomer | Immunotherapy (passive) | NCT04445831 | Active, not recruiting |”
§ Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update > Background > Anti-tau therapy
“ACI-35 is a liposome-based vaccine that targets pathological conformations of phosphorylated tau.”
Citations
Cites
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · cited 1×
“During the course of AD, many behavioral and psychological symptoms of dementia (BPSD) occur [2–4].”
BackgroundNIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · cited 1×
“However, activated microglia induce neurotoxic A1 astrocyte reactivity through the release of IL-1α, C1q, and TNF-α, resulting in a feedback loop of dysregulated inflammation in AD [28].”
BackgroundLecanemab 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
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · cited 1×
“The accumulation of NFTs might be initiated between the accumulation of Aβ and the development of clinical symptoms of AD [19].”
BackgroundThe precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431
Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial
Sims, J. R., Zimmer, J. A., Evans, C. D., Lu, M., Ardayfio, P., Sparks, J., Wessels, A. M., Shcherbinin, S., Wang, H., Monkul Nery, E. S., et al. (2023) · JAMA · doi:10.1001/jama.2023.13239 · Cited by 2,932 · cited 1×
“The study findings indicated the potential of donanemab to slow AD progression, particularly in the early stage [50].”
BackgroundThe molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708 · cited 2×
“In familial AD, mutant autosomal-dominant genes, including the genes for amyloid precursor protein ( APP ), presenilin-1 ( PSEN1 ), and presenilin-2 ( PSEN2 ), encode the major proteins involved in amyloid metabolism [13–15].”
Background
Research works printed but not linked: 1
- Reading CL, Ahlem CN, Murphy MF. NM101 Phase III study of NE3107 in Alzheimer’s disease: rationale, design and therapeutic modulation of neuroinflammation and insulin resistance. Neurodegener Dis Manag. 2021;11(4):289–98. · DOI · Paper page
Cited by
Sorted by citations
Items 101–200 of 250
Marra, C., Beccia, F., Caffarra, P., L’Abbate, F., Agosta, F., Benussi, A., Bonanni, L., Bruni, A. C., Bruno, G., Cappa, S. F., et al. (2025) · Neurological Sciences · doi:10.1007/s10072-025-08143-5 · Cited by 6
Dorababu, A. (2025) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2025.103606 · Cited by 5
Zhai, B., Hao, Q., Ming-fan, W., Luo, Z., Yang, R. Y., Yang, J. T., & Cao, Y. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107954 · Cited by 6
Safety Concerns in Neurological Clinical Trials: A Challenge That the FDA Must Resolve
Niazi, S. K. (2024) · Biomedicines · doi:10.3390/biomedicines12122918 · Cited by 4
Zhang, Z., Wang, W., Yang, X., et al. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01727-3 · Cited by 4
“Recently, efforts to treat AD with amy-loidosis-targeted drugs have failed [7].”
Jahani, S., Roshanaei, G., Tapak, L., & Initiative, A. D. N. (2025) · BMC Medical Research Methodology · doi:10.1186/s12874-025-02689-w · Cited by 7
Singh, A. S., Naqvi, A. R., & Chanu, M. T. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.01.050 · Cited by 7
Plasma Insulin Predicts Early Amyloid-β Pathology Changes in Alzheimer’s Disease
Chen, Y., Initiative, A. D. N., Wang, Z.-B., Liu, X., & Mao, Z. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240289 · Cited by 4
Microglial Drivers of Alzheimer's Disease Pathology: An Evolution of Diverse Participating States
Kuhn, M. K., & Proctor, E. A. (2024) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26723 · Cited by 5
“NE3107 is also in phase 3 trial, thought to exert a therapeutic effect through the inhibition of inflammatory ERK-and NF-κB signaling pathways [59, 60].”
Yan, J., Yang, X., Li, G., Ramírez, O. A., Hagenston, A. M., Chen, Z.-Y., & Bading, H. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03143-5 · Cited by 6
“However, therapeutic strategies aimed at interfering with the pathological processing of amyloid precursor protein and clearing amyloid β from the brain have yielded limited bene fi ts in clinical practice [2, 3].”
Mishra, A. K., Mishra, A., Kamal, Y. T., Kumar, A., Singh, H., Verma, S., & Khan, G. (2025) · Phytomedicine Plus · doi:10.1016/j.phyplu.2025.100877 · Cited by 4
Cicilien, N. P. Q., Ambamba, B. D. A., Ella, F. A., Injoh, A. N., Ngoumen, D. J. N., Mandob, D. E., & Ngondi, J. L. (2024) · Journal of Drug Delivery and Therapeutics · doi:10.22270/jddt.v14i1.6250 · Cited by 4
Diversity of amyloid beta peptide actions
Mardanyan, S. S., Sharoyan, S. G., & Antonyan, A. A. (2024) · Reviews in the Neurosciences · doi:10.1515/revneuro-2023-0100 · Cited by 5
Tsatali, M. S., Μoraitou, D., Gialaouzidis, M., Bakoglidou, E., Psaltis, V., Bertzes, N., Hassanin, H. I., Emmanouilidou, E., Totonidis, M., Frantzi, N., et al. (2024) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230151 · Cited by 4
Gavilán, E., Flores, A., Castaño, A., Martin-Presas, L., Bahatyrevich-Kharitonik, B., Medina-Guzman, R., Parrado, J., & Burguillos, M. Á. (2024) · Journal of Functional Foods · doi:10.1016/j.jff.2024.106220 · Cited by 6
“While in the field of Alzheimer ́ s disease (AD), recent clinical trials based on targeting the presence of A β plaques showed certain success (Huang et al., 2023), in the field of PD there has not been any therapeutic breakthrough, and current treatments aim to alleviate some of PD symptoms (Kalia…”
GNG5 is a novel regulator of Aβ42 production in Alzheimer’s disease
Li, C., Yang, Y., Luo, S., Qiu, W., Wang, X., & Ge, W. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07218-z · Cited by 4
“Additionally, only three monoclonal drugs, aducanumab, lecanemab and donanemab, have emerged from 38 discontinued drugs because of ineffectiveness and toxic side effects; their ef fi cacy remains under observation [30].”
Kang, H. S., Kim, J. H., Kim, J., Bang, W. J., Choi, H. G., Kim, N. Y., Park, H. Y., & Kwon, M. J. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13010260 · Cited by 4
“Notably, clinical trials are now underway to investigate the effectiveness of antibiotics and antiviral drugs in treating individuals with dementia [13].”
BackgroundScuteri, D., Pagliaro, M., Mantia, I., Contrada, M., Pignolo, L., Tonin, P., Nicotera, P., Bagetta, G., Corasaniti, M. T., & the Pilot BRAINAID Trial investigators (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1417851 · Cited by 4
“Despite progress, the main target remains the stage of amnestic mild cognitive impairment (aMCI) and prodromal AD (Huang et al., 2023).”
BackgroundRong, Y., Li, Q., Du, Y., Wang, W., Su, W., Zhang, J., & He, W. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1603861 · Cited by 3
Park, M., Ahn, J., Lim, J., Hwang, S., & Kim, K. (2025) · GeroScience · doi:10.1007/s11357-025-01869-2 · Cited by 4
“More than 55 million individuals worldwide are estimated to be affected by AD—the most prevalent cause of dementia—as of 2023, and this figure is projected to reach 82 million by 2030 and 150 million by 2050, with nearly 10 million new cases emerging each year [1–3].”
Waqar, Z., Sethi, P., Jain, D., Singh, K., Alsaidan, O. A., Alzarea, S. I., Gupta, J. K., Saxena, S., & Sharma, M. C. (2025) · Current Genomics · doi:10.2174/0113892029372437251010114053 · Cited by 6
“These patients will receive BIIB080 treatment for 36 weeks (NCT03186989) [175].”
Ren, S., Singh, J., Gsteiger, S., Cogley, C., Reed, B., Abrams, K. R., Dawoud, D., Owen, R. K., Tappenden, P., Quinn, T. J., et al. (2025) · Journal of Comparative Effectiveness Research · doi:10.57264/cer-2025-0095 · Cited by 5
“Our literature search also identified a review of ongoing phase II / III trials assessing the efficacy of anti-A β drugs in AD [50] .”
Antibody drug conjugates in Alzheimer’s disease: emerging strategies and future directions
AmeliMojarad, M., & AmeliMojarad, M. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.12.053 · Cited by 3
Brain-First vs. Body-First Models in Neurodegenerative Disease: A Perspective Review
Forte, G., & Casagrande, M. (2026) · NeuroSci · doi:10.3390/neurosci7030057 · Cited by 3
“Heart rate variability (HRV) provides a quantitative index of autonomic tone; reduced HRV indicates impaired parasympathetic modulation and correlates with prodromal Parkinson’s disease and Lewy body dementia [56], as well as appears to be related to cognitive deficit in MCI [10].”
Siam, N. H., Nasrin, N., Saiyara, S., Saha, H., Deb, D. P., & Islam, J. (2026) · Scientifica · doi:10.1155/sci5/6124916 · Cited by 3
Katola, F. O., Adana, M. Y., & Olajide, O. A. (2024) · Inflammation Research · doi:10.1007/s00011-024-01952-y · Cited by 4
“NE3107, a brain permeable anti-inflammatory drug which targets NF-κB mediated release of pro-inflammatory mediators is currently being investigated in Phase III clinical trials [7, 8].”
Sonsungsan, P., Aimauthon, S., Sriwichai, N., & Namchaiw, P. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e39378 · Cited by 5
“Currently, numerous drugs are in various stages of clinical trials and development [4,5].”
Neuroprotective Effect of Artemisinin in an Animal Model of Alzheimer’s Disease
Tiratsuyan, S., Hambardzumyan, Y., Poghosyan, M., Danielyan, M., & Hovhannisyan, A. A. (2024) · Current Medicinal Chemistry · doi:10.2174/0109298673312842241003111836 · Cited by 4
Sanami, S., Intzandt, B., Huck, J., Villeneuve, S., Iturria‐Medina, Y., & Gauthier, C. J. (2025) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2025.04.011 · Cited by 3
Popp, Z., Ang, T. F. A., Hwang, P. H., Au, R., & Chen, J. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251352216 · Cited by 3
“38 In this study, the majority of participants (86.9”
InfluentialUnveiling Aducanumab’s safety profile: A comprehensive pharmacovigilance analysis
Ji, H., Zhao, Z., & Zhao, C. (2025) · PLoS ONE · doi:10.1371/journal.pone.0328076 · Cited by 3
“Despite the potential benefits, the safety profile of Aducanumab requires rigorous evaluation, especially considering its impact on the central nervous system and the vulnerable patient population it serves [3].”
Recent Advancements in the Synthesis of Pyrazole Derivative for the Treatment of Alzheimer's Disease
Kumar, S., Paliwal, D., Sahu, R., & Kaushik, N. (2025) · Current Organic Chemistry · doi:10.2174/0113852728360592250214110907 · Cited by 5
Ramey, G. D., Tang, A., Phongpreecha, T., Yang, M. M., Woldemariam, S. R., Oskotsky, T., Montine, T. J., Allen, I. E., Miller, Z., Aghaeepour, N., et al. (2024) · medRxiv · doi:10.1101/2024.05.02.24306649 · Cited by 4
Combining GWAS Summary Data and Proteomics Identified Potential Drug Targets in Dementia
Zhao, Y., Lu, F., & Duan, Y. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04967-6 · Cited by 2
Biomarkers in Alzheimer’s disease: new frontiers with olfactory models
Maheshwari, S., Singh, A. V., & Verma, A. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-01705-1 · Cited by 3
Is screening for Alzheimer’s disease ready for prime time? Ask Wilson and Jungner
Chatanaka, M. K., Loren, M., & Diamandis, E. P. (2025) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2025.2533860 · Cited by 2
“Additional therapies are directed toward dementia with Lewy bodies and frontotemporal degeneration [39].”
Atractylenolide III alleviates amyloid-β-induced cognitive impairments in mice
Yuan, H., Xia, L., Li, J., Dai, C., Li, X., Xu, B., Xue, M., Shi, X., Wu, B., Dong, Z., et al. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10893-6 · Cited by 2
Lima, S. M., Moreira, G. D. C., Lins, A. C. D. A., Peixoto, A. L. D. A., & da Silva, J. C. (2025) · Research Society and Development · doi:10.33448/rsd-v14i8.49395 · Cited by 2
Saikat, S. N., & Siam, N. H. (2026) · Natural Products and Bioprospecting · doi:10.1007/s13659-026-00621-3 · Cited by 3
“Current evidence suggests that Aβ accumulation represents an early and critical event in disease pathogenesis, with fibrillar deposits appearing years often decades before visible clinical symptoms [6] The global health burden of AD continues to rise sharply.”
Barati, N., Shojaeian, A., Ramezani, M., Kalhori, F., Bazl, M. S. Y., Zafari, S., Asl, S. S., & Motavallihaghi, S. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114813 · Cited by 2
Hull, B., Miller, K. M., Corban, C., Backer, G., Sheehan, S., Korstanje, R., & Sutphin, G. L. (2024) · Biomolecules · doi:10.3390/biom14050599 · Cited by 2
Yang, M., Yan, C., Ospondpant, D., Wang, L., Lin, S., Tang, W. L., Dong, T. T.-X., Tong, P., Xu, Q., & Tsim, K. W. K. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1426569 · Cited by 2
Scuteri, D., Pierobon, D., Pagliaro, M., Hamamura, K., Hayashi, T., Pignolo, L., Nicotera, P., Bagetta, G., & Corasaniti, M. T. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16101253 · Cited by 2
Wang, P., Okada-Rising, S. L., Scultetus, A. H., & Bailey, Z. S. (2024) · Biomedicines · doi:10.3390/biomedicines12122698 · Cited by 4
Alghamdi, A., de Vos, S., Bos, J., Schuiling‐Veninga, C. C. M., Munster, B. C. V., Mubarik, S., Luijendijk, H. J., & Hak, E. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877241305799 · Cited by 2
Federated Multi-source Domain Adaptation via Vision Transformer for Multi-site Alzheimer’s Diagnosis
Cai, T., Lei, B., Yan, X., Wei, C., Liang, C., Xiao, X., Yang, Y., Wang, T., & Yang, P. (2025) · Lecture notes in computer science · doi:10.1007/978-981-96-3297-8_4 · Cited by 2
İğdeli, G., Fritzen, L., Pietrzik, C. U., & Temel, B. A. (2025) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2025.2486863 · Cited by 2
Khan, K. A., Esa, M., Kamal, Z., Ullah, B., Perry, G. L., Kamal, S., Ahmad, S., Hussain, H., Ullah, A., & Shafique, M. S. (2025) · Current Neuropharmacology · doi:10.2174/011570159x361867250313073624 · Cited by 2
Onda, K., Chotiyanonta, J. S., Cowley, H., Uchida, Y., Nowrangi, M. A., Adams, R., Lyketsos, C. G., Zandi, P. P., & Oishi, K. (2025) · International Psychogeriatrics · doi:10.1016/j.inpsyc.2025.100105 · Cited by 2
“While new treatments, such as anti-amyloid immunotherapies [7], are emerging, their effectiveness remains debated.”
Zhang, X., Zhou, J., Wu, H., & Guo, Y. (2025) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2025.2519867 · Cited by 3
“Tau aggregation inhibitors, including curcumin and methylene blue/LMTX, have advanced to phase 2 and 3 trials but have not demonstrated efficiency in disease treatment [5–8].”
Therapeutic Modalities Targeting Tau Protein in Alzheimer’s Disease
Schreiner, T. G., Iacob, L., Vasilache, C., & Schreiner, O. D. (2025) · Journal of dementia and Alzheimer's disease · doi:10.3390/jdad2030032 · Cited by 2
“A phase II trial (NCT05399888) focusing on cognitive outcomes in patients with mild cognitive impairment (MCI) or mild AD is underway and will conclude in December 2026 [56].”
Aging-Dependent Loss of Connectivity in Alzheimer’s Model Mice with Rescue by mGluR5 ModulatorPreprint
Mandino, F., Shen, X., Desrosiers-Grégoire, G., O’Connor, D. A., Mukherjee, B., Owens, A., Qu, A., Onofrey, J. A., Papademetris, X., Chakravarty, M. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.15.571715 · Cited by 2
“30 Further, this compound is known to modify AD course by rescuing synapses and improving memory, 31 and has recently entered clinical trials (ClinicalTrials.gov; NCT05804383).”
BackgroundGuarnier, G., Reinelt, J. D., Molloy, E. N., Mihai, P. G., Einaliyan, P., Valk, S. L., Modestino, A. E., Ugolini, M., Mueller, K., Wu, Q., et al. (2024) · medRxiv · doi:10.1101/2024.09.23.24314186 · Cited by 2
Molecular Mechanisms Associated with Neurodegeneration in Alzheimer's disease
de Hidalgo, U. M. D. S. N., Rodríguez, R. R., Estrada, L. E. R., et al. (2024) · International Journal of Medical Science and Clinical Research Studies · doi:10.47191/ijmscrs/v4-i02-17 · Cited by 1
Classification of Alzheimer Disease using Machine Learning Algorithm
Dasu, M. V., Priyanka, C., Tejaswini, G., Ramana, J. V., Suleman, D., & Sai, S. S. S. (2024) · International Conference on Automation and Computation (AUTOCOM) · doi:10.1109/autocom60220.2024.10486165 · Cited by 3
Fedotova, M. S., & Panfilova, H. (2024) · Social pharmacy in health care · doi:10.24959/sphhcj.24.316 · Cited by 1
Denner, T. C., Heise, N. V., Al‐Harrasi, A., et al. (2024) · Molecules · doi:10.3390/molecules29133015 · Cited by 1
Li, Q., Fu, Y., Cui, X.-J., Wang, Z.-T., Tan, L., & Initiative, A. D. N. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1339163 · Cited by 1
Emerging Alzheimer's disease treatment paradigms: A late‐stage clinical trial review
Hlávka, J. P., Kinoshita, A. T., Jeyasingh, D., Huang, C., Mirsafian, L., & Jacobson, M. (2024) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.70022 · Cited by 2
Current Drugs Used: Classification and Pharmacology
Swain, S. S., Mude, L., Roychowdhury, P., Karri, V. V. S. R., Kuppusamy, G., Gobinath, M., & Subramaniyan, V. (2024) · Springer eBooks · doi:10.1007/978-981-96-0259-9_8 · Cited by 1
Jeedi, N. M., Naik, R. R., Nimbal, S. K., & Patil, S. B. (2025) · Oriental Pharmacy and Experimental Medicine · doi:10.1007/s13596-025-00819-9 · Cited by 1
Li, R., Zi, J., Hu, Y., Li, X., Cao, Q., Li, Y., Wang, X., Xiong, J., & Cheng, G. (2025) · Rejuvenation Research · doi:10.1089/rej.2024.0092 · Cited by 2
Yesu, V. B., Rao, K. Y., Sajitha, K., Katta, V., Donka, S. B., Meti, M. D., More, U. A., Damu, A. G., & Srinivasulu, D. (2025) · Asian Journal of Chemistry · doi:10.14233/ajchem.2025.33493 · Cited by 1
Comparative pharmacokinetics and biodistribution of HAEE and HASS peptides
Ivanova, A., Lazareva, P. A., Kuzmichev, I., Vadekhina, V. V., Kosykh, A. V., Gurskaya, N. G., & Abakumov, M. A. (2025) · Bulletin of Russian State Medical University · doi:10.24075/brsmu.2025.036 · Cited by 1
Malarte, M., Chiotis, K., Ioannou, K., & Rodriguez‐Vieitez, E. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70222 · Cited by 2
Agarwal, U., Paliwal, S., Yadav, V., Pannu, A. S., Tonk, R. K., & Verma, S. K. (2025) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273402657250905055635 · Cited by 2
From the hive to the brain: synergistic potential of honeybee products with alzheimer’s drugs
El-Seedi, H. R., Salama, S. M., Shetaia, A. A., Elashal, M. H., El‐Wahed, A. A. A., Karav, S., Saeed, A., Alzahrani, M. A., Zou, X., Hriţcu, L., et al. (2025) · Metabolic Brain Disease · doi:10.1007/s11011-025-01727-2 · Cited by 1
“(Huang et al. 2023) in the brain of Alzheimer’s patients via the inhibition of nuclear factor-κB (NF-κB).”
InfluentialPolyphyletic screen defines distinct classes of plant-derived natural products that oppose tauopathy
Duangjan, C., Chang, X., Seidler, P. M., et al. (2025) · Life Science Alliance · doi:10.26508/lsa.202503393 · Cited by 1
Zothantluanga, J. H., Chagaleti, B. K., Roy, D., Abdalla, M., El‐Arabey, A. A., Alahmady, N. F., & Jha, N. K. (2026) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2026.108908 · Cited by 1
Srivastava, A., Narboshova, M., Banu, H., Thakur, S., Kasimova, X., & Karn, A. (2025) · International Conference on Information Systems and Computer Networks (ISCON) · doi:10.1109/iscon65210.2025.11340797 · Cited by 1
Gu, S., Yin, W., Xie, M., He, C., Bian, Y., Li, L., Lu, W., & Wang, Q. (2026) · Chinese Herbal Medicines · doi:10.1016/j.chmed.2026.02.003 · Cited by 1
Ahmad, H. A., Zafar, M., Khan, T., & Khan, M. I. (2026) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-026-05505-1 · Cited by 1
“[13].”
Lin, Y., Hsu, T., Kao, Y., Thompson, T., Carvalho, A. F., Stubbs, B., Tseng, P., Hsu, C., Yang, F.-C., Tsai, C., et al. (2026) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2025-336691 · Cited by 1
Jiang, E., Ullah, S., Waheed, I., Han, J., & Zhang, X. (2026) · Clinical Interventions in Aging · doi:10.2147/cia.s585864 · Cited by 2
“83 Animal studies indicate that HTN causes cerebral small vessel disease (CSVD), which is linked to higher Aβ and tau levels.”
Khan, S., Prinsa, Bano, N., Fazal, F., Ahamad, S., Saha, S., Dar, N. J., & Bhat, S. A. (2026) · Network Modeling Analysis in Health Informatics and Bioinformatics · doi:10.1007/s13721-026-00776-6 · Cited by 1
Myeong, S. H., Lee, N. K., Lee, N.-H., et al. (2026) · Stem Cell Research & Therapy · doi:10.1186/s13287-026-04958-x · Cited by 1
“Despite the recent FDA approvals of lecanemab and donanemab, the clinical benefits are modest, and concerns about amyloid-related imaging abnormalities persist [4–6].”
Naringenin-loaded nanoparticles ameliorate scopolamine-induced neurotoxicity
Alqarni, A., Abd-Elghany, A. A., Bedewi, M. A., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-44225-w · Cited by 1
“Over 55 million people worldwide are presently affected by conditions like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and other dementias; a new case is discovered every three seconds 2 .”
CTAD 2025: Key trends redefining therapeutic and diagnostic strategies in Alzheimer's disease
Yuan, M., & Zhou, H.-Y. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261430764 · Cited by 1
“18 This trend translates “ ultra-early intervention ” from a theoretical concept into a feasible trial paradigm, potentially informing regulatory pathways for even earlier patient inclusion.”
Shah, M., Sinha, S., Bhasme, M., Yadav, M. R., & Nagani, A. (2026) · The Chemical Record · doi:10.1002/tcr.70137 · Cited by 1
Singh, A., Sahu, S. K., & Sah, A. K. (2026) · BioMed Research International · doi:10.1155/bmri/5968529 · Cited by 1
Biscetti, L., Gambuzza, M. E., Princiotto, M., Sabbatinelli, J., Olivieri, F., Fiorillo, M., Chinigò, C., Muglia, L., Cozza, A., Beccacece, A., et al. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119326 · Cited by 2
Saha, T., Vats, T., & Mehan, S. (2026) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2026.2671714 · Cited by 2
“Activated microglia release il-1α, c1q, and tNF-α, which lead to astrocyte activation and create a feedback loop of dysregulated inflammation in AD [192].”
Masi, M., Oliviero, C., Govoni, S. M., Wolozin, B. L., Racchi, M., & Buoso, E. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179033 · Cited by 2
Cheng, M., Zheng, X., Wei, Y.-D., & Ge, J. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179152 · Cited by 1
Essa, M., Ahmed, N., Kakar, A., Akber, W., Barech, S., Farooq, A., & Mumtaz, T. (2024) · doi:10.32948/ajsep.2024.03.28 · Cited by 1
Zolkiffly, S. Z. I., Hasan, M. H., Jusoh, S. A., Janakiraman, A. K., Eshak, Z., Kumar, S. S., & Chellammal, H. S. J. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177967 · Cited by 1
Pankov, D. I., Terekhov, R. P., Rakhimov, A., Dzuban, A. V., Утенышев, А. Н., Shilov, G. V., & Selivanova, I. A. (2025) · Farmaciya (Pharmacy) · doi:10.29296/25419218-2025-05-02 · Cited by 1
Adeola, H. A., & Robinson, R. A. S. (2025) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.5c00074 · Cited by 1
Li, Y., Zhu, Y., & Yao, M. (2023) · Human Brain · doi:10.37819/hb.2.1770
Ferritin Nanocage-Enabled Detection of Pathological Tau in Living Human Retinal CellsPreprint
Barolo, L., Gigante, Y., Mautone, L., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3931244/v1
Trends in incidence, mortality, dynamic needs and rapid evolution of healthcare in dementia
Ma, K., & Hu, C. (2024) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2024.105389
Self-citationAlzheimer's disease - a review of medicinal substances and their derivatives
Więcek, M., Piotrowska, D. G., Kołodziejczyk, M. K., & Głowacka, I. E. (2024) · Farmacja Polska · doi:10.32383/farmpol/185732
PD-1/PD-L1 Inhibitors for Alzheimer’s Pathology: A Literature ReviewPreprint
HUANG, S. F., Long, Y., Lau, K., & Nagpal, B. (2024) · doi:10.31234/osf.io/hf9y3
Limb Speed Perception Accuracy in Neurodegenerative Disease
Brandmeir, C. L. (2024) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.12362
Суслов, Н. И., Сергеевна, Ф. Ю., & Коробов, М. Л. (2024) · Research Results in Pharmacology · doi:10.18413/rrpharmacology.10.489
Advances in Developing Small Molecule Drugs for Alzheimer's Disease
Zhang, W., Zhang, L., Lv, M., Fu, Y., Meng, X., Wang, M., & Wang, H. (2024) · Current Alzheimer Research · doi:10.2174/0115672050329828240805074938 · Cited by 1
Bibliometric Analysis of Research Between Deep Brain Stimulation and Alzheimer’s Disease
Cabanillas‐Lazo, M., Quispe‐Vicuña, C., Espinoza‐Carhuancho, F., & Mayta-Tovalino, F. (2024) · International journal of Nutrition Pharmacology Neurological Diseases · doi:10.4103/ijnpnd.ijnpnd_121_24
Clinical trials for neurodegenerative diseases
Paneyala, S., Yambao, P. E. L., Syed, J. M., Pura, M. A. B., & Roque, J. C. V. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-28822-7.00022-2
Global amyloid burden enhances network efficiency of tau propagation in the brain
Lauber, M. V., Bellitti, M., Kapadia, K., Jasodanand, V. H., Au, R., & Kolachalama, V. B. (2024) · Journal of Alzheimer s Disease · doi:10.1177/13872877241294084
Murshid, N. M., Sahardi, N. F. N. M., & Makpol, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms26010241
Metadata
- Authors
- Huang, L.-K., Kuan, Y.-C., Lin, H.-W., & Hu, C.-J.
- Affiliations
- Taipei Medical University-Shuang Ho Hospital (TW)
- National Taiwan University (TW)
- Taipei Medical University (TW)
- Corresponding author
- Hu, Chaur-Jong
- Venue
- Journal of Biomedical Science
- Published
- 2023-10-02
- Volume
- 30
- Issue
- 1
- Pages
- 83-83
- ISSN
- 1021-7770 (ISSN-L)
- 1423-0127
- PMC
- PMC10544555
- OpenAlex
- W4387259038
- Semantic Scholar
- c0688229e547b86cdf80c6678871dd16ba30491e
- Cited by
- 252
- References
- 86
- Citations by year
- 2026: 54 · 2025: 88 · 2024: 105 · 2023: 5
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Journal of Biomedical Science (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, clinical trials, new drug development, aducanumab, lecanemab, disease-modifying therapy, amyloid accumulation, neuroinflammation, clinical trial design
- MeSH terms
- Alzheimer Disease, Humans, Amyloid beta-Peptides
About these checks
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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
