ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Apolipoprotein E moderates the association between non-APOE polygenic risk score for Alzheimer's disease and aging on preclinical cognitive function.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 9 citations in OpenAlex.
- Polygenicity and APOE ε4 shape response to intervention in mild cognitive impairment.Alzheimer's research & therapy · 2025Trial
- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- APOE ε4 and Accelerated Cognitive Decline Among Cognitively Healthy Middle-Aged and Older Adults.JAMA network open · 2026Article
- Amyloid-Frontiers in aging neuroscience · 2026Article
- PreoperativeFrontiers in bioinformatics · 2026Review
- Toward personalized medicine in AD/ADRD through genetic-exposome dementia risk assessments.NPJ dementia · 2026Review
- Polygenic risk for Alzheimer's disease in healthy aging: age-related and APOE-driven effects on brain structures and cognition.Genome medicine · 2025Article
- Plasma proteomics for risk prediction of Alzheimer's disease in the general population.Aging cell · 2024Article
- Mid-to-Late Life Healthy Lifestyle Modifies Genetic Risk for Longitudinal Cognitive Aging among Asymptomatic Individuals.medRxiv : the preprint server for health sciences · 2024Article
- Apolipoprotein E moderates the association between non-APOE polygenic risk score for Alzheimer's disease and aging on preclinical cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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7 authors at 2 institutions in 1 country.
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Abstract
introductionVariation in preclinical cognitive decline suggests additional genetic factors related to Alzheimer's disease (eg, a non-APOE polygenic risk score [PRS]) may interact with the APOE ε4 allele to influence cognitive decline.
methodsWe tested the PRS × APOE ε4 × age interaction on preclinical cognition using longitudinal data from the Wisconsin Registry for Alzheimer's Prevention. All analyses were fitted using a linear mixed-effects model and adjusted for within individual/family correlation among 1190 individuals.
resultsWe found statistically significant PRS × APOE ε4 × age interactions on immediate learning (P = 0.038), delayed recall (P < 0.001), and Preclinical Alzheimer's Cognitive Composite 3 score (P = 0.026). PRS-related differences in overall and memory-related cognitive domains between people with and without APOE ε4 emerge around age 70, with a much stronger adverse PRS effect among APOE ε4 carriers. The findings were replicated in a population-based cohort. DISCUSSIONS: APOE ε4 can modify the association between PRS and cognition decline. HIGHLIGHTS: APOE ε4 can modify the association between polygenic risk scores (PRSs) and longitudinal cognition decline, with the modifying effects more pronounced when the PRS is constructed using a conservative P threshold (eg, P < 5
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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.