Evidence map›Paper›PMID 29843241›Full record

ReviewJournal of Alzheimer's disease : JAD2018

The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade.

Erika N Cline, Maíra Assunção Bicca, Kirsten L Viola, William L Klein

Open access · hybridAbstract readReview
In one paragraph

Review in Journal of Alzheimer's disease : JAD, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 456 papers.

0numbers the graph read from it
0cells of the map it votes in
456citing papers in PubMed
46.2field-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

456 citing papers in PubMed, 836 citations in OpenAlex.

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  19. bioRxiv : the preprint server for biology · 2026
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396 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

4 authors at 2 institutions in 1 country.

Erika N ClineDepartment of Neurobiology, Cognitive Neurology and Alzheimer's Disease Center, International Institute for Nanotechnology, and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
Maíra Assunção BiccaDepartment of Neurobiology, Cognitive Neurology and Alzheimer's Disease Center, International Institute for Nanotechnology, and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
Kirsten L ViolaDepartment of Neurobiology, Cognitive Neurology and Alzheimer's Disease Center, International Institute for Nanotechnology, and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
William L KleinDepartment of Neurobiology, Cognitive Neurology and Alzheimer's Disease Center, International Institute for Nanotechnology, and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
International Institute for NanotechnologyNorthwestern University · US

Funding

PREDOCTORAL AND POSTDOCTORAL TRAINING PROGRAM IN AGING AND DEMENTIAT32AG020506 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ROBERT J VASSAR, SANDRA WEINTRAUB · 2002 to 2026
$9.9M
Development of a non-fibrillic amyloid-beta oligomer selective positron emission tomography imaging diagnostic for Alzheimer.R41AG054337 · NIA · ACUMEN PHARMACEUTICALS, INC. · PI KLEIN, WILLIAM L · 2016 to 2016
$222k
NIA NIH HHS R41 AG054337NIA NIH HHS T32 AG020506
6 · The paper itself

Abstract

The amyloid-β oligomer (AβO) hypothesis was introduced in 1998. It proposed that the brain damage leading to Alzheimer's disease (AD) was instigated by soluble, ligand-like AβOs. This hypothesis was based on the discovery that fibril-free synthetic preparations of AβOs were potent CNS neurotoxins that rapidly inhibited long-term potentiation and, with time, caused selective nerve cell death (Lambert et al., 1998). The mechanism was attributed to disrupted signaling involving the tyrosine-protein kinase Fyn, mediated by an unknown toxin receptor. Over 4,000 articles concerning AβOs have been published since then, including more than 400 reviews. AβOs have been shown to accumulate in an AD-dependent manner in human and animal model brain tissue and, experimentally, to impair learning and memory and instigate major facets of AD neuropathology, including tau pathology, synapse deterioration and loss, inflammation, and oxidative damage. As reviewed by Hayden and Teplow in 2013, the AβO hypothesis "has all but supplanted the amyloid cascade." Despite the emerging understanding of the role played by AβOs in AD pathogenesis, AβOs have not yet received the clinical attention given to amyloid plaques, which have been at the core of major attempts at therapeutics and diagnostics but are no longer regarded as the most pathogenic form of Aβ. However, if the momentum of AβO research continues, particularly efforts to elucidate key aspects of structure, a clear path to a successful disease modifying therapy can be envisioned. Ensuring that lessons learned from recent, late-stage clinical failures are applied appropriately throughout therapeutic development will further enable the likelihood of a successful therapy in the near-term.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsHumansModels, NeurologicalAmyloid beta-PeptidesAlzheimer’s diseaseamyloid-β peptidediagnosticsetiologymodel systemsoligomersprionsreceptorsstructure-functiontautherapeutics

Identifiers

PMID29843241
PMCPMC6004937
OpenAlexW2809078375

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.