Association of polygenic risk scores with Alzheimer's disease and plasma biomarkers among Chinese older adults: A community‐based study

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 .