Alzheimer's disease polygenic risk scores were associated with vascular pathologies, which partially mediated the effect of genetic risk on late-life cognition.
Observational (n=2,907)
Genetic risk for Alzheimer's disease, primarily driven by the APOE gene, overlaps with vascular pathologies that partially mediate its effect on late-life cognition.
INTRODUCTION: We sought to examine the genetic overlap between vascular pathologies and Alzheimer's disease (AD) dementia, and the potential mediating role of vascular pathologies between AD-related genetic variants and late-life cognition. METHODS: For 2907 stroke-free older individuals, we examined the association of polygenic risk scores for AD dementia (ADPRSs) with vascular pathologies and with cognition. Mediation analyses addressed whether association between ADPRSs and cognition was mediated by a vascular pathology. RESULTS: ADPRSs were associated with lobar cerebral microbleeds, white matter lesion load, and coronary artery calcification, mostly explained by single nucleotide polymorphisms in the 19q13 region. The effect of ADPRSs on cognition was partially but significantly mediated by cerebral microbleeds, white matter lesions, and coronary artery calcification. DISCUSSION: Our findings provide evidence for genetic overlap, mostly due to apolipoprotein E (APOE) gene, between vascular pathologies and AD dementia. The association between AD polygenic risk and late-life cognition is mediated in part via effects on vascular pathologies.
Lin et al. (Tue,) conducted a observational in Alzheimer's disease dementia and vascular pathologies (n=2,907). Polygenic risk scores for Alzheimer's disease dementia (ADPRSs) was evaluated on Association of ADPRSs with vascular pathologies and cognition. Alzheimer's disease polygenic risk scores were associated with vascular pathologies, which partially mediated the effect of genetic risk on late-life cognition.