ArticleAlzheimer's research & therapy2025
Development of a Japanese polygenic risk score model for amyloid-β PET imaging in Alzheimer's disease.
Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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7 authors.
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Abstract
backgroundThe use of polygenic risk scores (PRS) for predicting disease risk in Japanese populations, particularly for dementia and related phenotypes, remains markedly unexplored. The aim of this study was to bridge this gap by developing a novel PRS model designed to predict amyloid-β (Aβ) deposition utilizing positron emission tomography (PET) imaging data from a Japanese cohort.
methodsUsing the polygenic risk score-continuous shrinkage (PRS-CS) algorithm, we calculated PRS based on significant single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) in this population. We applied a PRS calculation approach informed by Japanese genome-wide association studies (GWAS) summary statistics into a Japanese dementia cohort from Keio University.
resultsOur findings revealed that a p-value threshold of pT < 0.1 optimally enhanced the predictive capability of the Japanese Aβ PET positivity risk model. Moreover, we demonstrated that distinguishing between the counts of APOE2 and APOE4 alleles in our calculations significantly elevated model performance, achieving an area under the curve (AUC) of 0.759. Remarkably, this predictive accuracy remained robust even when the pT was adjusted to be < 1.0 × 10
conclusionsThese findings highlight the potential of PRS as a noninvasive tool for early detection and risk stratification of AD, which could lead to enhanced clinical applications and interventions.
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