Alzheimer's polygenic risk scores are associated with cognitive phenotypes in Down syndrome

INTRODUCTION: This study aimed to investigate the influence of the overall Alzheimer's disease (AD) genetic architecture on Down syndrome (DS) status, cognitive measures, and cerebrospinal fluid (CSF) biomarkers. METHODS: AD polygenic risk scores (PRS) were tested for association with DS-related traits. RESULTS: The AD risk PRS was associated with disease status in several cohorts of sporadic late- and early-onset and familial late-onset AD, but not in familial earlyonset AD or DS. On the other hand, lower DS Mental Status Examination memory scores were associated with higher PRS, independent of intellectual disability and APOE (PRS including APOE, PRSAPOE, p = 2.84 x 10(-4); PRS excluding APOE, PRSnonAPOE, p = 1.60 x 10(-2)). PRSAPOE exhibited significant associations with A beta 42, tTau, pTau, and A beta 42/40 ratio in DS. DISCUSSION: These data indicate that the AD genetic architecture influences cognitive and CSF phenotypes in DS adults, supporting common pathways that influence memory decline in both traits.

Automated summary

This study investigates the influence of Alzheimer's disease genetic architecture on Down syndrome status, cognitive measures, and cerebrospinal fluid biomarkers. The results suggest that the AD genetic architecture influences cognitive and CSF phenotypes in DS adults, supporting common pathways that influence memory decline in both traits.