Genetic Predisposition to Alzheimer's Disease Is Associated with Enlargement of Perivascular Spaces in Centrum Semiovale Region

Abstract

ALFA Study.-- This article belongs to the Special Issue Genetic Research of Neurodegenerative and Psychiatric Disorders. ; This study investigated whether genetic factors involved in Alzheimer's disease (AD) are associated with enlargement of Perivascular Spaces (ePVS) in the brain. A total of 680 participants with T2-weighted MRI scans and genetic information were acquired from the ALFA study. ePVS in the basal ganglia (BG) and the centrum semiovale (CS) were assessed based on a validated visual rating scale. We used univariate and multivariate logistic regression models to investigate associations between ePVS in BG and CS with BIN1-rs744373, as well as APOE genotypes. We found a significant association of the BIN1-rs744373 polymorphism in the CS subscale (p value = 0.019; OR = 2.564), suggesting that G allele carriers have an increased risk of ePVS in comparison with A allele carriers. In stratified analysis by APOE-ε4 status (carriers vs. non-carriers), these results remained significant only for ε4 carriers (p value = 0.011; OR = 1.429). To our knowledge, the present study is the first suggesting that genetic predisposition for AD is associated with ePVS in CS. These findings provide evidence that underlying biological processes affecting AD may influence CS-ePVS. ; The project leading to these results has received funding from "la Caixa" Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004, the Alzheimer's Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17-519007) and the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016-2020 grant# SLT002/16/00201). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892. All CRG authors acknowledge the support of the Spanish Ministry of Science, Innovation and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme / Generalitat de Catalunya. JDG is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054). NV-T is funded by a postdoctoral grant, Juan de la Cierva Programme (FJC2018-038085-I), Ministry of Science and Innovation—Spanish State Research Agency. ; Peer reviewed