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

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}.