ReviewNeuron2022
ApoE Cascade Hypothesis in the pathogenesis of Alzheimer's disease and related dementias.
Review in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 1 of them a synthesis that pooled 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.
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
186 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cognitive Functioning of Unaffected First-degree Relatives of Individuals With Late-onset Alzheimer's Disease: A Systematic Literature Review and Meta-analysis.Neuropsychology review · 2023Pooled it
- Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease.The journal of prevention of Alzheimer's disease · 2026Trial
- Genetic Prioritization of Plasma Proteins Across Dementia Subtypes: A Proteome-Wide Mendelian Randomization and Bayesian Colocalization Analysis.Cellular and molecular neurobiology · 2026Article
- Fibronectin mediates APOE4-driven blood-brain barrier dysfunction in Alzheimer's disease.Nature aging · 2026Article
- Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Zika virus infection induces a persistent accumulation of Alzheimer's disease-like Tau phosphorylation in adult immunocompetent mice in association with memory and social behavior impairments.Acta neuropathologica communications · 2026Article
- TDP-43 dysfunction facilitates the pathological conversion of tau.Molecular neurodegeneration · 2026Article
- Short-lived Niemann-Pick type C mice with accelerated brain aging as a novel model for Alzheimer's disease research.Neural regeneration research · 2026Article
- Alzheimer disease protection from the periphery.Nature reviews. Neurology · 2026Article
- Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- Integrative machine learning approach to risk prediction for dementia and Alzheimer's disease.GeroScience · 2026Article
- Amyloid-related imaging abnormalities (ARIA) in Alzheimer's disease: from pathophysiology to individualized risk assessment.Alzheimer's research & therapy · 2026Review
- Molecular characterization of humanized APOE mouse models reveals source and genotype dependent differences.Molecular neurodegeneration · 2026Article
- The metabolic roots of memory loss: interlinking the Diabetes-Alzheimer's hypothesis.Metabolic brain disease · 2026Review
- Clinical Associations and Possible Risk Factors for Affective Neuropsychiatric Symptoms in Older Adults With and Without Cognitive Impairment.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2026Article
- Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy.Science (New York, N.Y.) · 2026Article
- Regulation of Lipid Dysmetabolism and Neuroinflammation Progression Linked With Alzheimer's Disease Through Modulation of Dgat2.Aging cell · 2026Article
126 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
8 authors.
Funding
Abstract
The ε4 allele of the apolipoprotein E gene (APOE4) is a strong genetic risk factor for Alzheimer's disease (AD) and several other neurodegenerative conditions, including Lewy body dementia (LBD). The three APOE alleles encode protein isoforms that differ from one another only at amino acid positions 112 and 158: apoE2 (C112, C158), apoE3 (C112, R158), and apoE4 (R112, R158). Despite progress, it remains unclear how these small amino acid differences in apoE sequence among the three isoforms lead to profound effects on aging and disease-related pathways. Here, we propose a novel "ApoE Cascade Hypothesis" in AD and age-related cognitive decline, which states that the biochemical and biophysical properties of apoE impact a cascade of events at the cellular and systems levels, ultimately impacting aging-related pathogenic conditions including AD. As such, apoE-targeted therapeutic interventions are predicted to be more effective by addressing the biochemical phase of the cascade.
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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.