ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2023
AD and non-AD mediators of the pathway between the APOE genotype and cognition.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- The concurrent burden of Alzheimer's pathology, cerebral amyloid angiopathy, and microinfarcts on cognitive decline.The journal of prevention of Alzheimer's disease · 2026Article
- Article
- Apolipoprotein E and Alzheimer's disease pathology in a diverse autopsy study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Mediation of the Association BetweenNeurology · 2025Article
- The interplay between age at menopause and synaptic integrity on Alzheimer's disease risk in women.Science advances · 2025Article
- Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries.JAMA network open · 2025Article
- Association between Apolipoprotein E gene polymorphism and the tortuosity of extracranial carotid artery.Frontiers in neurology · 2025Article
- Multisite chronic pain: association with cognitive decline and post-mortem Alzheimer's biomarkers.Brain communications · 2025Article
- Multifaceted roles of APOE in Alzheimer disease.Nature reviews. Neurology · 2024Review
- Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.Acta neuropathologica communications · 2023Review
- Social determinants of health, genetic biomarkers, and cognitive function in Chinese older adults with subjective cognitive decline and mild cognitive impairment: A cross-sectional analysis.Journal of Alzheimer's disease reportsArticle
- Article
Corrections and comments
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Authors and funding
12 authors at 10 institutions in 2 countries.
Funding
Abstract
introductionThe apolipoprotein E (APOE) genotype is a driver of cognitive decline and dementia. We used causal mediation methods to characterize pathways linking the APOE genotype to late-life cognition through Alzheimer's disease (AD) and non-AD neuropathologies.
methodsWe analyzed autopsy data from 1671 individuals from the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study (ROS/MAP/MARS) studies with cognitive assessment within 5 years of death and autopsy measures of AD (amyloid beta (Aβ), neurofibrillary tangles), vascular (athero/arteriolo-sclerosis, micro-infarcts/macro-infarcts), and non-AD neurodegenerative neuropathologies (TAR DNA protein 43 [TDP-43], Lewy bodies, amyloid angiopathy, hippocampal sclerosis).
resultsThe detrimental effect of APOE ε4 on cognition was mediated by summary measures of AD and non-AD neurodegenerative neuropathologies but not vascular neuropathologies; effects were strongest in individuals with dementia. The protective effect of APOE ε2 was partly mediated by AD neuropathology and stronger in women than in men. DISCUSSION: The APOE genotype influences cognition and dementia through multiple neuropathological pathways, with implications for different therapeutic strategies targeting people at increased risk for dementia. HIGHLIGHTS: Both apolipoprotein E (APOE) ε2 and APOE ε4 effects on late-life cognition are mediated by AD neuropathology. The estimated mediated effects of most measures of AD neuropathology were similar. Non-Alzheimer's disease (AD) neurodegenerative pathologies mediate the effect of ε4 independently from AD. Non-AD vascular pathologies did not mediate the effect of the APOE genotype on cognition. The protective effect of APOE ε2 on cognition was stronger in women.
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