Relationships between frontal metabolites and Alzheimer's disease biomarkers in cognitively normal older adults

Neurobiol Aging. 2022 Jan:109:22-30. doi: 10.1016/j.neurobiolaging.2021.09.016. Epub 2021 Sep 20.

Abstract

Elevated expression of β-amyloid (Aβ1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aβ1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.

Keywords: Aging; Alzheimer's disease; Cerebrospinal fluid biomarkers; Frontal cortex; General cognition; Magnetic resonance spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging / metabolism*
  • Aging / physiology*
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Cognition*
  • Creatine / metabolism
  • Female
  • Frontal Lobe / metabolism*
  • Humans
  • Inositol / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Peptide Fragments / cerebrospinal fluid*
  • gamma-Aminobutyric Acid / metabolism
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Aspartic Acid
  • Inositol
  • gamma-Aminobutyric Acid
  • N-acetylaspartate
  • Creatine