Associations between baseline amyloid, sex, and APOE on subsequent tau accumulation in cerebrospinal fluid

Neurobiol Aging. 2019 Jun;78:178-185. doi: 10.1016/j.neurobiolaging.2019.02.019. Epub 2019 Mar 7.


We investigated the effect of baseline Aβ, sex, and APOE on longitudinal tau accumulation in cerebrospinal fluid (CSF) in clinically normal older adults. Two hundred thirty-nine participants (aged 56-89 years, clinical dementia rating = 0) underwent serial CSF collection for Aβ1-42, total-tau (t-tau) and phospho-tau181P (p-tau). We used preprocessed data from fully automated Roche Elecsys immunoassays. A series of linear regressions were used to examine cross-sectional effects of Aβ1-42, sex, and APOEε4 on baseline CSF tau and linear mixed models for longitudinal changes in CSF tau. Cross-sectionally, CSF t-tau and p-tau were associated with abnormal Aβ1-42 and APOEε4 but not with sex. Longitudinally, low baseline CSF Aβ1-42 levels, but not APOEε4 or sex, predicted faster p-tau accumulation. The relationship between baseline CSF Aβ1-42 and tau accumulation was strongest in APOEε4 carriers, and particularly female carriers, relative to other groups. The current findings support an association between baseline CSF Aβ1-42 and changes in CSF tau. Elevated risk in females, apparent only in carriers, reinforces findings of sex-related vulnerability in those with genetic predisposition for Alzheimer's disease.

Keywords: APOE; Alzheimer's disease; Amyloid; Cerebrospinal fluid; Sex; tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Apolipoproteins E / genetics*
  • Cross-Sectional Studies
  • Female
  • Genetic Predisposition to Disease / genetics
  • Healthy Aging / cerebrospinal fluid*
  • Heterozygote*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Risk
  • Sex Characteristics*
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins