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

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.

The etiology and evolution of magnetic resonance imaging-visible perivascular spaces: Systematic review and meta-analysis

“…Our study has some limitations: First, a wide variety of imaging methods and MVPVS evaluation methods have been employed to assess MVPVS. Even within studies, the interrater agreement for MVPVS detection can be moderate to substantial (Cohen’s kappa: 0:58–0.91) ( Wang et al, 2019 ; Best et al, 2020 ; Javierre-Petit et al, 2020 ; Ciampa et al, 2021 ; Song et al, 2021 ). This heterogeneity could have biased our narrative summary.…”

Enlarged Perivascular Spaces and Age-Related Clinical Diseases

“…61 In addition to the clearance mechanism of brain metabolic waste, some scholars have also elaborated on the relationship between EPVSs and AD from the perspective of tau pathophysiology, neurodegeneration, and synaptic dysfunction 62 or AD gene susceptibility. 63 Some studies have indicated that βamyloidosis and EPVSs in patients with AD are not associated with PET findings. 60 The Influence of Other Markers on the Assessment of EPVSs Should Not Be Ignored…”

Advances in brain barriers and brain fluids research in 2021: great progress in a time of adversity

“…Gertje et al [ 73 ] found that enlargement of these spaces was associated with small vessel disease, but their data did not support a role in the early stages of Alzheimer’s disease pathology. In contrast, Paradise et al [ 74 ] found that severe perivascular space dilation was associated with increased chance of cognitive decline and dementia and Ciampa et al [ 75 ] reported that genetic risk factors for Alzheimer’s disease are associated with enlarged perivascular spaces in the centrum semiovalae region of the brain.…”