Evidence map›Paper›PMID 35177833›Full record

ReviewNature reviews. Drug discovery2022

The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics.

Eric Karran, Bart De Strooper

Open access · greenAbstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Drug discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 376 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
376citing papers in PubMed, 5 pooled it
74.4field-weighted citation impact, top 1% of its field
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

376 citing papers in PubMed, 5 syntheses or guidelines pooled it, 660 citations in OpenAlex.

  1. Practical Brain MRI Guidelines for Anti-Aβ Antibody Treatment in Early Symptomatic Alzheimer's Disease.Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine · 2025
    Guideline
  2. Guideline
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

316 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 3 countries.

Eric KarranCambridge Research Center, AbbVie, Inc., Cambridge, MA, USA. eric.karran@abbvie.com.ORCID http://orcid.org/0000-0002-6782-5213
Bart De StrooperVIB Centre for Brain Disease Research, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0001-5455-5819
AbbVie (United States) · USUK Dementia Research Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many drugs that target amyloid-β (Aβ) in Alzheimer disease (AD) have failed to demonstrate clinical efficacy. However, four anti-Aβ antibodies have been shown to mediate the removal of amyloid plaque from brains of patients with AD, and the FDA has recently granted accelerated approval to one of these, aducanumab, using reduction of amyloid plaque as a surrogate end point. The rationale for approval and the extent of the clinical benefit from these antibodies are under intense debate. With the aim of informing this debate, we review clinical trial data for drugs that target Aβ from the perspective of the temporal interplay between the two pathognomonic protein aggregates in AD - Aβ plaques and tau neurofibrillary tangles - and their relationship to cognitive impairment, highlighting differences in drug properties that could affect their clinical performance. On this basis, we propose that Aβ pathology drives tau pathology, that amyloid plaque would need to be reduced to a low level (~20 centiloids) to reveal significant clinical benefit and that there will be a lag between the removal of amyloid and the potential to observe a clinical benefit. We conclude that the speed of amyloid removal from the brain by a potential therapy will be important in demonstrating clinical benefit in the context of a clinical trial.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBrainHumansNeurofibrillary TanglesPlaque, Amyloidtau ProteinsAmyloid beta-Peptidestau Proteins

Identifiers

PMID35177833
OpenAlexW4213065543

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.