Evidence map›Paper›PMID 25231068›Full record

ReviewActa neuropathologica communications2014

Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer's disease.

Gary P Morris, Ian A Clark, Bryce Vissel

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Acta neuropathologica communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 283 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
283citing papers in PubMed, 4 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

283 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Pooled it
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  5. Trial
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  7. Article
  8. SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Review
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  15. Complex interplay of astrogliosis and pathology in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  16. Review
  17. The evolving landscape of amyloid-targeting therapies in Alzheimer's disease: progress and challenges.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
  18. Article
  19. Article
  20. Review

223 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

3 authors.

Gary P Morris
Ian A Clark
Bryce VisselGarvan Institute of Medical Research, Neuroscience Department, Neurodegenerative Disorders Laboratory, 384 Victoria Street, Darlinghurst 2010, NSW, Australia. brycevissel@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The amyloid hypothesis has driven drug development strategies for Alzheimer's disease for over 20 years. We review why accumulation of amyloid-beta (Aβ) oligomers is generally considered causal for synaptic loss and neurodegeneration in AD. We elaborate on and update arguments for and against the amyloid hypothesis with new data and interpretations, and consider why the amyloid hypothesis may be failing therapeutically. We note several unresolved issues in the field including the presence of Aβ deposition in cognitively normal individuals, the weak correlation between plaque load and cognition, questions regarding the biochemical nature, presence and role of Aβ oligomeric assemblies in vivo, the bias of pre-clinical AD models toward the amyloid hypothesis and the poorly explained pathological heterogeneity and comorbidities associated with AD. We also illustrate how extensive data cited in support of the amyloid hypothesis, including genetic links to disease, can be interpreted independently of a role for Aβ in AD. We conclude it is essential to expand our view of pathogenesis beyond Aβ and tau pathology and suggest several future directions for AD research, which we argue will be critical to understanding AD pathogenesis.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesHumansNeurofibrillary TanglesPlaque, AmyloidSynapsestau ProteinsAmyloid beta-Peptidestau Proteins

Identifiers

PMID25231068
PMCPMC4207354

What OpenQuestion holds

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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.