Evidence map›Paper›PMID 39468148›Full record

SynthesisScientific reports2024

Critical assessment of anti-amyloid-β monoclonal antibodies effects in Alzheimer's disease: a systematic review and meta-analysis highlighting target engagement and clinical meaningfulness.

Konstantinos I Avgerinos, Apostolos Manolopoulos, Luigi Ferrucci, Dimitrios Kapogiannis

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Volume change with gantenerumab: Impact of amyloid-related imaging abnormalities and amyloid removal.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Trial
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  7. Review
  8. Review
  9. Review
  10. Classification of tau status with machine learning models in amyloid-positive cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  11. Beyond the Cochrane review: Re-evaluating anti-amyloid therapy in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  12. Recent Cochrane review has serious flaws: A perspective of clinicians and researchers from around the world.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Konstantinos I AvgerinosDepartment of Neurology, Wayne State University, Detroit Medical Center, University Health Center, 8th floor, 4201 St. Antoine, Detroit, MI, 48201, USA.
Apostolos ManolopoulosIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, 21224, USA.
Luigi FerrucciIntramural Research Program, Longitudinal Studies Section, National Institute on Aging, NIH, 251 Bayview Blvd, Ste 8C228, Baltimore, MD, 21224, USA.
Dimitrios KapogiannisIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, 21224, USA. kapogiannisd@mail.nih.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite most monoclonal antibodies against Aβ in Alzheimer's failed to demonstrate efficacy, the newest antibodies showed statistically significant clinical effects. We conducted a systematic review and meta-analysis to assess the efficacy, target engagement, and safety of anti-Aβ antibodies in sporadic AD including phase III RCTs published up to November 28, 2023. Antibodies as a drug class, attenuated worsening on the clinical scales CDR-SB and ADAS-Cog by very small effect sizes and reduced amyloid on PET by a very large effect size. Reduction of amyloid on PET was moderately correlated with CDR-SB and ADAS-Cog reductions. However, antibodies increased risk of ARIA-E and ARIA-H by a very large and moderate effect size, respectively. In subgroup analyses by individual drug, Donanemab and Lecanemab induced the largest benefits. In subgroup analyses by binding affinity, antibodies without binding to monomers were associated with the most favorable effects. Despite statistical significance for improvement on clinical measures, antibody effects were below the threshold of clinically meaningful change during the period they were studied. However, the newest antibodies demonstrably interfere with the underlying ΑD pathophysiology and therefore their benefit could be cumulative over time leading to larger clinical effects in subsequent years. PROSPERO registration no. CRD42022381334.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAntibodies, MonoclonalHumansPositron-Emission TomographyTreatment OutcomeAmyloid beta-PeptidesAntibodies, Monoclonal

Identifiers

PMID39468148
PMCPMC11520896

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.