ArticleAlzheimer's & dementia (New York, N. Y.)
Pathway-based polygenic risk of Alzheimer's disease highlights immune genes in cognitive decline.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Functionally informed annotation influences pathway-specific polygenic risk and disease inference in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- PreoperativeFrontiers in bioinformatics · 2026Review
- 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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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
introductionAlzheimer's disease (AD) is a genetically heterogeneous disease, with various genetic variants potentially influencing disease mechanisms differently. Pathway-based polygenic risk scores (p-PRS) can be used to examine how groups of risk genes with similar biological functions impact disease-related endophenotypes such as cognitive decline. potentially aiding in differentiating pre-clinical dementia from normal age-related cognitive decline.
methodsData from 1,737 participants (53.5% female) from the Betula study were analyzed. AD-weighted p-PRS were calculated for five AD-related pathways: immune response, tau, cholesterol, protein-lipid, and amyloid. The p-PRS were tested for associations with all-cause dementia risk (
resultsAll-cause dementia risk was significantly predicted by the gw- and immune PRS. Hazard ratios for gw-, immune-, tau-, cholesterol-, and amyloid p-PRS were larger for prediction of AD risk and smaller for VD risk relative to all-cause dementia, while the opposite was seen for the protein-lipid p-PRS. Cognitive decline was stronger associated with the immune p-PRS than the gw-PRS, and this effect was driven by participants that remained non-demented (linear age-effects). Amyloid p-PRS showed accelerated age-effect at the oldest age in both non-demented and subsequently demented. DISCUSSION: Our results show that AD-weighted p-PRS have differential roles on dementia risk and cognitive decline. Specifically, results suggest a broad role of immune p-PRS in both age-related cognitive decline and dementia risk, while amyloid p-PRS influences AD risk and pre-clinical cognitive decline, and protein-lipid p-PRS does not influence AD risk nor cognitive decline but show a potential role in VD. Results are of value for development of precision medicine based on genetic risk profiling. Highlights: All-cause dementia and Alzheimer's disease (AD) risk is strongest predicted by apolipoprotein E (
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