Dataset Information

Genetic overlap between vascular pathologies and Alzheimer's dementia and potential causal mechanisms.

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.

SUBMITTER: Lin YF

PROVIDER: S-EPMC6435328 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Genetic overlap between vascular pathologies and Alzheimer's dementia and potential causal mechanisms.

Lin Yen-Feng YF Smith Albert Vernon AV Aspelund Thor T Betensky Rebecca A RA Smoller Jordan W JW Gudnason Vilmundur V Launer Lenore J LJ Blacker Deborah D

Alzheimer's & dementia : the journal of the Alzheimer's Association 20180919 1

<h4>Introduction</h4>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.<h4>Methods</h4>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 cogni ...[more]

PMID: 30240575

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Dataset Information

Genetic overlap between vascular pathologies and Alzheimer's dementia and potential causal mechanisms.

Introduction

Methods

Results

Discussion

Publications

Genetic overlap between vascular pathologies and Alzheimer's dementia and potential causal mechanisms.

Similar Datasets

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