ArticleJournal of Alzheimer's disease : JAD2023
Effect of Pathway-Specific Polygenic Risk Scores for Alzheimer's Disease (AD) on Rate of Change in Cognitive Function and AD-Related Biomarkers Among Asymptomatic Individuals.
Article in Journal of Alzheimer's disease : JAD, 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, 13 citations in OpenAlex.
- DiscoDivas: Leveraging genetic-ancestry continuum information to interpolate PRS for admixed populations.American journal of human genetics · 2026Article
- Functionally informed annotation influences pathway-specific polygenic risk and disease inference in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- APOE ε4 and Accelerated Cognitive Decline Among Cognitively Healthy Middle-Aged and Older Adults.JAMA network open · 2026Article
- Sex-specific early cognitive changes are linked to global and pathway-specific genetic risk for Alzheimer's disease in at-risk individuals.Biology of sex differences · 2026Article
- Predictive Biomarkers for Asymptomatic Adults: Opportunities, Risks, and Guidance for General Practice.Diagnostics (Basel, Switzerland) · 2026Review
- DiscoDivas: Leveraging genetic ancestry continuum information to interpolate PRS for admixed populations.medRxiv : the preprint server for health sciences · 2025Article
- Advances in Genetic Risk Scores for Alzheimer's Disease and Dementia: A Systematic Review.Neurology international · 2025Review
- Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population.International journal of molecular sciences · 2025Article
- 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
- Apolipoprotein E moderates the association between Non-medRxiv : the preprint server for health sciences · 2023Article
- Pathway-based polygenic risk of Alzheimer's disease highlights immune genes in cognitive decline.Alzheimer's & dementia (New York, N. Y.)Article
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15 authors at 6 institutions in 5 countries.
Funding
Abstract
backgroundGenetic scores for late-onset Alzheimer's disease (LOAD) have been associated with preclinical cognitive decline and biomarker variations. Compared with an overall polygenic risk score (PRS), a pathway-specific PRS (p-PRS) may be more appropriate in predicting a specific biomarker or cognitive component underlying LOAD pathology earlier in the lifespan.
objectiveIn this study, we leveraged longitudinal data from the Wisconsin Registry for Alzheimer's Prevention and explored changing patterns in cognition and biomarkers at various age points along six biological pathways.
methodsPRS and p-PRSs with and without APOE were constructed separately based on the significant SNPs associated with LOAD in a recent genome-wide association study meta-analysis and compared to APOE alone. We used a linear mixed-effects model to assess the association between PRS/p-PRSs and cognitive trajectories among 1,175 individuals. We also applied the model to the outcomes of cerebrospinal fluid biomarkers in a subset. Replication analyses were performed in an independent sample.
resultsWe found p-PRSs and the overall PRS can predict preclinical changes in cognition and biomarkers. The effects of PRS/p-PRSs on rate of change in cognition, amyloid-β, and tau outcomes are dependent on age and appear earlier in the lifespan when APOE is included in these risk scores compared to when APOE is excluded.
conclusionIn addition to APOE, the p-PRSs can predict age-dependent changes in amyloid-β, tau, and cognition. Once validated, they could be used to identify individuals with an elevated genetic risk of accumulating amyloid-β and tau, long before the onset of clinical symptoms.
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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.