ReviewNature reviews. Neuroscience2022
The probabilistic model of Alzheimer disease: the amyloid hypothesis revised.
Review in Nature reviews. Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
271 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Alzheimer's Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD): Executive summary of recommendations for specialty care.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Guideline
- p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial.Nature medicine · 2024Trial
- Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer's disease.Alzheimer's research & therapy · 2023Trial
- Dementia in type 2 diabetes: risk factors, disease processes and opportunities for prevention across the lifespan.Diabetologia · 2026Review
- Prospect in Alzheimer's disease integrative therapy targeting both amyloid-beta and tau.Neural regeneration research · 2026Article
- Integrating frailty into decision-making for disease-modifying therapies in Alzheimer's disease: a proposed expert-opinion based approach.The journal of prevention of Alzheimer's disease · 2026Review
- PLCG2 downregulation impairs synaptic function and increases Alzheimer's disease hallmarks in neuronal cultures.Nature genetics · 2026Article
- Alzheimer's disease-like brain pattern biomarker: capturing risks and predicting disease onset.Molecular psychiatry · 2026Article
- Distinct Transcriptional States of TDP-43 Pathology in an Alzheimer's Disease Mouse Model.Neuroscience bulletin · 2026Article
- Association of Alzheimer's disease blood-based biomarkers and visit-to-visit blood pressure variability: The HABS-HD study.Journal of Alzheimer's disease : JAD · 2026Article
- Cognitive heterogeneity in mild cognitive impairment due to Alzheimer's disease pathology.Neural regeneration research · 2026Article
- Algal bioactive compounds for next-generation biopesticides: a multi-target resource for sustainable pest management.Environmental science and pollution research international · 2026Review
- Neural networks and econometric models: Advancing brain connectivity for Alzheimer's drug development.Neural regeneration research · 2026Article
- Modular brain networks shape amyloid-driven tau spread and cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Which assessment tools best distinguish between mild cognitive impairment and dementia? Lessons from a Slovak memory clinic cohort.BMC geriatrics · 2026Article
- Just Semantics? How Diagnostic Criteria Influence Physician-Patient Narratives in Alzheimer's Disease.Neuro-degenerative diseases · 2026Article
- Article
- Raman Spectroscopy for Probing Pathological Protein Aggregates: Potential and Perspectives for Advanced Diagnostic Applications.International journal of molecular sciences · 2026Review
- Defining Alzheimer's disease: stipulations and the ethics of diagnostic change.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Modeling Alzheimer's disease through the integration of exposome, inflammasome, and connectome.Neural regeneration research · 2026Article
211 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, in which a deterministic chain of events leads from amyloid deposition and then tau deposition to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging information regarding the complex biology of AD and the challenges of developing amyloid-targeting drugs, the amyloid hypothesis needs to be reconsidered. Here we propose a probabilistic model of AD in which three variants of AD (autosomal dominant AD, APOE ε4-related sporadic AD and APOE ε4-unrelated sporadic AD) feature decreasing penetrance and decreasing weight of the amyloid pathophysiological cascade, and increasing weight of stochastic factors (environmental exposures and lower-risk genes). Together, these variants account for a large share of the neuropathological and clinical variability observed in people with AD. The implementation of this model in research might lead to a better understanding of disease pathophysiology, a revision of the current clinical taxonomy and accelerated development of strategies to prevent and treat AD.
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Registered trials
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.