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

Genes (Basel). 2021 May 27;12(6):825. doi: 10.3390/genes12060825.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01835717.

Keywords: APOE-ε4; BIN1-rs744373; enlargement of perivascular spaces; neurogenetics; virchow robin spaces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Aged
  • Alzheimer Disease / genetics*
  • Apolipoproteins E / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Glymphatic System / diagnostic imaging*
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Tumor Suppressor Proteins / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • ApoE protein, human
  • Apolipoproteins E
  • BIN1 protein, human
  • Nuclear Proteins
  • Tumor Suppressor Proteins

Associated data

  • ClinicalTrials.gov/NCT01835717