Genetic overlap between vascular pathologies and Alzheimer's dementia and potential causal mechanisms. Issue 1 (18th September 2018)

• Record Type: Journal Article
• Authors: Lin, Yen‐Feng; Smith, Albert Vernon; Aspelund, Thor; Betensky, Rebecca A.; Smoller, Jordan W.; Gudnason, Vilmundur; Launer, Lenore J.; Blacker, Deborah
• Is Part Of: Alzheimer's & dementia. Volume 15:Issue 1(2019)
• Page Start: 65
• Page End: 75
• Publication Date: 2018-09-18
• Subjects: Alzheimer's dementia -- Polygenic risk score -- Cerebral microbleeds -- White matter lesions -- Coronary calcification -- Cognitive impairment -- Causal mediation; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2018.08.002
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: 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.