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
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Statistics
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- 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.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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.
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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.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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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
“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.
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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.
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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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- 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
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“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
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“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
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Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
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“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
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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].”
BackgroundNeurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
Amyloid deposition as the central event in the aetiology of Alzheimer’s disease
Hardy, J., & Allsop, D. (1991) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(91)90609-v · Cited by 2,538
A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Feldman, H. H., Frisoni, G. B., Hampel, H., Jagust, W. J., Johnson, K. A., Knopman, D. S., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000002923 · Cited by 1,864 · cited 1×
“The analysis of a combination of biomarkers such as amyloid, tau, and neurodegeneration (collectively, ATN classification) has been proposed by research on AD [24, 25].”
BackgroundDonanemab in Early Alzheimer’s Disease
Mintun, M. A., Lo, A. C., Duggan Evans, C., Wessels, A. M., Ardayfio, P. A., Andersen, S. W., Shcherbinin, S., Sparks, J., Sims, J. R., Brys, M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2100708 · Cited by 1,728 · cited 4×
“The trial started in October 2022; 1,500 participants will be recruited by using the same criteria as those of TRAILBLAZER-ALZ 2 from 148 sites across China, Korea, Taiwan, and Europe; and the trial is expected to run until mid-2025.”
BackgroundInfluentialNeuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · cited 1×
“NFTs and quantitative neuronal loss may be more closely correlated with disease severity and dementia progression than the amyloid plaque burden [20–22].”
BackgroundThe spectrum of behavioral changes in Alzheimer's disease
Mega, M., Cummings, J., Fiorello, T., & Gornbein, J. (1996) · Neurology · doi:10.1212/wnl.46.1.130 · Cited by 1,124
Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease
Honig, L. S., Vellas, B., Woodward, M., Boada, M., Bullock, R., Borrie, M., Hager, K., Andreasen, N., Scarpini, E., Liu-Seifert, H., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1705971 · Cited by 1,049 · cited 2×
“Similarly, the phase 3 trial EXPEDITION-3 demonstrated that 400 mg solanezumab administered every 4 weeks did not have significant effects on cognitive decline in patients with mild AD [52].”
BackgroundLecanemab: Appropriate Use Recommendations
Cummings, J., Apostolova, L., Rabinovici, G. D., Atri, A., Aisen, P., Greenberg, S., Hendrix, S., Selkoe, D., Weiner, M., Petersen, R. C., et al. (2023) · The Journal of Prevention of Alzheimer's Disease · doi:10.14283/jpad.2023.30 · Cited by 961 · cited 1×
“The appropriate use recommendations (AURs) for lecanemab and aducanumab highlight the importance of patient selection, surveillance for adverse events, and clinician preparedness [44, 45].”
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 2×
“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] A double-blind, placebocontrolled phase 2 trial recruited 856 patients with AD with mild cogni…”
BackgroundRaina, P., Santaguida, P., Ismaila, A., Patterson, C., Cowan, D., Levine, M., Booker, L., & Oremus, M. (2008) · Annals of Internal Medicine · doi:10.7326/0003-4819-148-5-200803040-00009 · Cited by 771 · cited 1×
“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].”
BackgroundThe Evolution of Preclinical Alzheimer’s Disease: Implications for Prevention Trials
Sperling, R., Mormino, E., & Johnson, K. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.038 · Cited by 725 · cited 1×
“Cerebral Aβ fibril deposition may occur decades before the onset of clinical symptoms [8].”
BackgroundClinical trials of new drugs for Alzheimer disease
Huang, L.-K., Chao, S.-P., & Hu, C.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0609-7 · Cited by 702 · cited 1×
“However, the targets of both phase 1 and phase 2 trials are diverse, with a noticeable increase in the number of phase 1 trials focusing on neuroprotection and phase 2 trials focusing on anti-neuroinflammation [85].”
BackgroundSelf-citationLian, H., Yang, L., Cole, A., Sun, L., Chiang, A. C.-A., Fowler, S. W., Shim, D. J., Rodriguez-Rivera, J., Taglialatela, G., Jankowsky, J. L., et al. (2015) · Neuron · doi:10.1016/j.neuron.2014.11.018 · Cited by 697 · cited 1×
“Subsequently, by binding to C3a receptors, C3 causes neuronal dysfunction and microglial activation [27].”
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 · cited 1×
“BPDO-1603 is a potential cognitive-enhancing drug for AD, but its mechanism of action remains unknown [61].”
BackgroundLee, J.-H., Yang, D.-S., Goulbourne, C. N., Im, E., Stavrides, P., Pensalfini, A., Chan, H., Bouchet-Marquis, C., Bleiwas, C., Berg, M. J., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01084-8 · Cited by 638 · cited 1×
“These formations constitute the primary source of the majority of amyloid plaques found in mouse models of AD [35].”
BackgroundAlzheimer's disease drug development pipeline: 2017
Cummings, J., Lee, G., Mortsdorf, T., Ritter, A., & Zhong, K. (2017) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.05.002 · Cited by 549
Hamelin, L., Lagarde, J., Dorothée, G., Leroy, C., Labit, M., Comley, R. A., de Souza, L. C., Corne, H., Dauphinot, L., Bertoux, M., et al. (2016) · Brain · doi:10.1093/brain/aww017 · Cited by 519 · cited 1×
“The excessive accumulation of Aβ or other toxic compounds activates proinflammatory phenotypes, resulting in neuronal damage [29].”
BackgroundNeocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease
Bierer, L. M., Hof, P. R., Purohit, D. P., Carlin, L., Schmeidler, J., Davis, K. L., & Perl, D. P. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540250089017 · Cited by 514 · cited 1×
“NFTs and quantitative neuronal loss may be more closely correlated with disease severity and dementia progression than the amyloid plaque burden [20–22].”
BackgroundThe amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy
McGeer, P. L., & McGeer, E. G. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1177-7 · Cited by 467 · cited 1×
“The inadequate clearance of Aβ along with the aggregation of tau disrupts microglial defense mechanisms, resulting in sustained and harmful microglial activation [32].”
BackgroundFrequency of hippocampal formation atrophy in normal aging and Alzheimer's disease
De Leon, M. J., George, A. E., Golomb, J., Tarshish, C., Convit, A., Kluger, A., De Santi, S., Mc Rae, T., Ferris, S. H., Reisberg, B., et al. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00213-8 · Cited by 429 · cited 1×
“Brain atrophy, particularly in the hippocampus, is major indicator of early Aβ accumulation, particularly in the presubiculum [9, 10].”
BackgroundNeuronal Cell Death Mechanisms in Major Neurodegenerative Diseases
Chi, H., Chang, H.-Y., & Sang, T.-K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103082 · Cited by 412 · cited 1×
“Neuroprotective therapies, including free radical scavengers, regeneration enhancers, and the suppression of excitable amino acid signaling pathways, have been proposed for preventing neuronal death or brain atrophy caused by amyloid, tau, and neuroinflammation [36].”
BackgroundStructural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β
Arndt, J. W., Qian, F., Smith, B. A., Quan, C., Kilambi, K. P., Bush, M. W., Walz, T., Pepinsky, R. B., Bussière, T., Hamann, S., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-24501-0 · Cited by 369 · cited 1×
“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].”
BackgroundA trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease
Salloway, S., Farlow, M., McDade, E., Clifford, D. B., Wang, G., Llibre-Guerra, J. J., Hitchcock, J. M., Mills, S. L., Santacruz, A. M., Aschenbrenner, A. J., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01369-8 · Cited by 359 · cited 4×
“Both trials (NCT03887455 and NCT01760005) had a overall low risk of bias [43, 53, 83, 84].”
BackgroundResultInfluentialBateman, R. J., Benzinger, T. L., Berry, S., Clifford, D. B., Duggan, C., Fagan, A. M., Fanning, K., Farlow, M. R., Hassenstab, J., McDade, E. M., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.07.005 · Cited by 303 · cited 3×
“Both trials (NCT03887455 and NCT01760005) had a overall low risk of bias [43, 53, 83, 84].”
BackgroundResultApostolova, L. G. (2016) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000307 · Cited by 277
Tucker, S., Möller, C., Tegerstedt, K., Lord, A., Laudon, H., Sjödahl, J., Söderberg, L., Spens, E., Sahlin, C., Waara, E. R., et al. (2015) · Journal of Alzheimer’s Disease · doi:10.3233/jad-140741 · Cited by 272 · cited 1×
“Lecanemab (brand name: Leqembi), a humanized IgG1 antibody derived from mAb158, selectively binds to soluble Aβ protofibrils [40].”
BackgroundPontecorvo, M. J., Lu, M., Burnham, S. C., Schade, A. E., Dage, J. L., Shcherbinin, S., Collins, E. C., Sims, J. R., & Mintun, M. A. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.3392 · Cited by 261
Approval 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 1×
“Further trials must be conducted to confirm the potential benefit of aducanumab [39].”
BackgroundXiao, S., Chan, P., Wang, T., Hong, Z., Wang, S., Kuang, W., He, J., Pan, X., Zhou, Y., Ji, Y., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00795-7 · Cited by 224
Beyreuther, K., & Masters, C. L. (1991) · Brain Pathology · doi:10.1111/j.1750-3639.1991.tb00667.x · Cited by 221 · cited 1×
“Aβ accumulation was discovered to be crucial by three independent research groups in 1991 [11–13].”
BackgroundShcherbinin, S., Evans, C. D., Lu, M., Andersen, S. W., Pontecorvo, M. J., Willis, B. A., Gueorguieva, I., Hauck, P. M., Brooks, D. A., Mintun, M. A., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.2793 · Cited by 210 · cited 1×
“Amyloid burden reduction was correlated with improvement in iADRS scores only in ApoE4 carriers [48].”
BackgroundAducanumab: Appropriate Use Recommendations Update
Cummings, J. L., Rabinovici, G. D., Atri, A., Aisen, P. S. S., Apostolova, L. G., Hendrix, S. B., Sabbagh, M. N., Selkoe, D. J., Weiner, M. W., & Salloway, S. (2022) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2022.34 · Cited by 204 · cited 1×
“The appropriate use recommendations (AURs) for lecanemab and aducanumab highlight the importance of patient selection, surveillance for adverse events, and clinician preparedness [44, 45].”
BackgroundThe precursor of Alzheimer??s disease amyloid A4 protein resembles a cell-surface receptor
Kang, J.-M., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Kh, G., Multhaup, G., Beyreuther, K. T., & Müller‐Hill, B. (1987) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-198701030-00032 · Cited by 194
Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease
Herrmann, N., Ruthirakuhan, M. T., Gallagher, D., Verhoeff, N. P. L. G., Kiss, A., Black, S. E., & Lanctôt, K. L. (2019) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2019.05.002 · Cited by 182 · cited 1×
“Nabilone is a partial agonist of cannabinoid receptor 1 (CB1) and CB2 in the brain and in peripheral tissues, and it has been reported to provide effective treatment for agitation in patients with AD [78].”
BackgroundTau Proteins and Neurofibrillary Degeneration
Goedert, M., Spillantini, M. G., & Crowther, R. A. (1991) · Brain Pathology · doi:10.1111/j.1750-3639.1991.tb00671.x · Cited by 178 · cited 1×
“Although the exact causes of AD remain unclear, the disease has two pathological hallmarks: plaques composed of amyloid-beta (Aβ) fibrils and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau protein [5–7].”
BackgroundThe role of extracellular Tau in the spreading of neurofibrillary pathology
Medina, M., & Avila, J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00113 · Cited by 161 · cited 1×
“As the disease progresses, the gradual spread of tau pathology throughout brain regions has been suggested to be caused by the transfer of abnormal types of tau protein from one neuron to another [18].”
BackgroundPost-mortem analysis of neuroinflammatory changes in human Alzheimer’s disease
Gomez-Nicola, D., & Boche, D. (2015) · Alzheimer's Research & Therapy · doi:10.1186/s13195-015-0126-1 · Cited by 147 · cited 1×
“Sustained inflammation has been observed in the brains of patients with AD [30, 31].”
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“The participants were offered an open-label extension with high-dose gan-tenerumab 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.”
BackgroundNilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer’s Disease
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“Sustained inflammation has been observed in the brains of patients with AD [30, 31].”
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“GLP-1 receptors are involved in cognition, synaptic transmission in hippocampal neurons, and cell apoptosis; thus, they may serve as targets for exploring candidate drugs with neuroprotective and cognition-enhancing effects [72].”
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“CT1812 is a ligand that targets the component 1 subunit of the sigma2/progesterone membrane receptor.”
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“Buntanetap is a novel translational inhibitor of multiple neurotoxic proteins, including APP, tau, and α-synuclein, by enhancing the binding of the atypical iron response element in the 5′UTR regions of the mRNA of the neurotoxic proteins to iron regulatory protein 1 [62].”
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“activity and the insulin receptor substrate/glycogen synthase kinase-3β signaling pathway [79].”
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“Until recently, treatment options were limited to managing symptoms, but approvals for disease-modifying drugs for AD and genetic forms of ALS point to considerable progress 2,3 .”
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“Some clinical trials have shown promising results, such as improved cognitive function and reduced inflammatory markers following probiotic supplementation [142,143].”
Background
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
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