Effects of amyloid pathology and the APOE ε4 allele on the association between cerebrospinal fluid Aβ38 and Aβ40 and brain morphology in cognitively normal 70-years-olds

Neurobiol Aging. 2021 May:101:1-12. doi: 10.1016/j.neurobiolaging.2020.10.033. Epub 2021 Jan 12.

Abstract

The association between cerebrospinal fluid (CSF) amyloid beta (Aβ) Aβ38 or Aβ40 and brain grey- and white matter integrity is poorly understood. We studied this in 213 cognitively normal 70-year-olds, and in subgroups defined by presence/absence of the APOE ε4 allele and Aβ pathology: Aβ-/APOE-, Aβ+/APOE-, Aβ-/APOE+ and Aβ+/APOE+. CSF Aβ was quantified using ELISA and genotyping for APOE was performed. Low CSF Aβ42 defined Aβ plaque pathology. Brain volumes were assessed using Freesurfer-5.3, and white matter integrity using tract-based statistics in FSL. Aβ38 and Aβ40 were positively correlated with cortical thickness, some subcortical volumes and white matter integrity in the total sample, and in 3 of the subgroups: Aβ-/APOE-, Aβ+/APOE- and Aβ-/APOE+. In Aβ+/APOE+ subjects, higher Aβ38 and Aβ40 were linked to reduced cortical thickness and subcortical volumes. We hypothesize that production of all Aβ species decrease in brain regions with atrophy. In Aβ+/APOE+, Aβ-dysregulation may be linked to cortical atrophy in which high Aβ levels is causing pathological changes in the gray matter of the brain.

Keywords: Amyloid-beta-38; Amyloid-beta-40; Cognitively normal; Diffusion-tensor-imaging; Structural-magnetic-resonance-imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / pathology*
  • Aging / physiology
  • Aging / psychology*
  • Alleles*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Apolipoprotein E4 / genetics*
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Cognition*
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Male

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4