Abstract
INTRODUCTION: We examined the associations of polygenic risk score (PRS) with Alzheimer's disease (AD) and plasma biomarkers in the Chinese population. METHODS: This population-based study used baseline data from MIND-China (2018; n = 4873) and follow-up data from dementia-free individuals (2014-2018; n = 2117). We measured AD-related plasma biomarkers in a subsample (n = 1256). Data were analyzed using logistic and Cox regression models. RESULTS: We developed PRS with (PRS(APOE)) and without (PRS(non-) (APOE)) apolipoprotein E (APOE) gene. In the longitudinal analysis, PRS(APOE) was associated with a multivariable-adjusted hazards ratio of 1.91 (95% CI = 1.13-3.23) for AD. PRS(APOE) in combination with demographics yielded discriminative (area under the curve [AUC]) and predictive(C-statistic) accuracy of 0.80 (95% confidence interval [CI] = 0.77-0.84) and 0.80 (0.77-0.82), respectively. PRS(non-) (APOE) showed an association with AD risk similar to PRS(APOE). PRS(APOE), but not PRS(non-) (APOE), was associated with reduced plasma Aβ42/Aβ40 ratio and increased Neurofilament light chain (NfL) (p < 0.05). DISCUSSION: The PRS with and without APOE gene, in combination with demographics, shows good discriminative and predictive ability for AD. The AD-related pathologies underlie AD risk associated with PRS(APOE). HIGHLIGHTS: The PRS(APOE) and PRS(non-) (APOE) were associated with AD risk in the Chinese population. The PRS(APOE) and PRS(non-) (APOE), in combination with demographics, showed good discriminative and predictive ability for AD. The AD-related pathologies underlie the AD risk associated with PRS(APOE) but not PRS(non-) (APOE).