Cortical thickness is differently associated with ALDH2 rs671 polymorphism according to level of amyloid deposition

Sci Rep. 2021 Sep 30;11(1):19529. doi: 10.1038/s41598-021-98834-8.

Abstract

Accumulating evidence indicates that amyloid-beta (Aβ) deposition and biogenic aldehyde accumulation contribute to the pathogenesis of neurodegenerative diseases. Human aldehyde dehydrogenase 2 (ALDH2) metabolizes biogenic aldehydes produced in the brain to prevent damage. However, r671G>A, a single nucleotide polymorphism of ALDH2, causes aldehyde accumulation and decreased ALDH2 activity. We aimed to investigate whether Aβ deposition and rs671 polymorphism have an interaction effect on cortical thickness (CTh). We grouped 179 participants in the Biobank Innovations for chronic Cerebrovascular disease With ALZheimer's disease Study as follows: amyloid (-) [A(-)] and amyloid (+) [A(+)] groups based on the Aβ deposition degree; A-carrier (AC) and GG (GG) groups based on the presence/absence of the rs671 A allele; and their combinations, i.e., A(-)AC, A(-)GG, A(+)AC, and A(+)GG groups. A multiple regression analysis identified nine regions of interest. Compared with the A(-)GG group, the A(-)AC group showed thinner CTh in all regions. There were no significant differences between the A(+)AC and A(+)GG groups. We observed an interaction effect of amyloid deposition and rs671 polymorphism on CTh. The CTh in the A(-) group appeared to be strongly influenced by rs671 polymorphism, which could have contributed to cortical thinning and biogenic aldehyde accumulation in the AC group. Additionally, CTh in the A(+) group appeared to be strongly influenced by amyloid deposition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aldehyde Dehydrogenase, Mitochondrial / genetics*
  • Alleles*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Biomarkers
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology*
  • Cognition
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size
  • Polymorphism, Single Nucleotide*
  • Positron-Emission Tomography

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Biomarkers
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase, Mitochondrial