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

Abstract

INTRODUCTIONWe examined the associations of polygenic risk score (PRS) with Alzheimer's disease (AD) and plasma biomarkers in the Chinese population.METHODSThis 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.RESULTSWe developed PRS with (PRSAPOE) and without (PRSnon‐APOE) apolipoprotein E (APOE) gene. In the longitudinal analysis, PRSAPOE was associated with a multivariable‐adjusted hazards ratio of 1.91 (95% CI = 1.13–3.23) for AD. PRSAPOE 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. PRSnon‐APOE showed an association with AD risk similar to PRSAPOE. PRSAPOE, but not PRSnon‐APOE, was associated with reduced plasma Aβ42/Aβ40 ratio and increased Neurofilament light chain (NfL) (p < 0.05).DISCUSSIONThe 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 PRSAPOE.Highlights The PRSAPOE and PRSnon‐APOE were associated with AD risk in the Chinese population. The PRSAPOE and PRSnon‐APOE, in combination with demographics, showed good discriminative and predictive ability for AD. The AD‐related pathologies underlie the AD risk associated with PRSAPOE but not PRSnon‐APOE.