Genetic overlap between vascular pathologies and Alzheimer's dementia and potential causal mechanisms.
Alzheimers Dement
; 15(1): 65-75, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-30240575
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Microvasos
/
Enfermedad de Alzheimer
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Alzheimers Dement
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos