Evidence map›Paper›PMID 26007212›Full record

ReviewNature neuroscience2015

The case for rejecting the amyloid cascade hypothesis.

Karl Herrup

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 354 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
354citing papers in PubMed, 3 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

354 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Non-microglial downregulation ofbioRxiv : the preprint server for biology · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Review

294 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

1 author.

Karl Herrup1] Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong. [2] State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Kowloon, Hong Kong.ORCID 0000000177865844

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is a biologically complex neurodegenerative dementia. Nearly 20 years ago, with the combination of observations from biochemistry, neuropathology and genetics, a compelling hypothesis known as the amyloid cascade hypothesis was formulated. The core of this hypothesis is that it is pathological accumulations of amyloid-β, a peptide fragment of a membrane protein called amyloid precursor protein, that act as the root cause of AD and initiate its pathogenesis. Yet, with the passage of time, growing amounts of data have accumulated that are inconsistent with the basically linear structure of this hypothesis. And while there is fear in the field over the consequences of rejecting it outright, clinging to an inaccurate disease model is the option we should fear most. This Perspective explores the proposition that we are over-reliant on amyloid to define and diagnose AD and that the time has come to face our fears and reject the amyloid cascade hypothesis.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsHumansModels, NeurologicalAmyloid beta-Peptides

Identifiers

PMID26007212

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.