APOE differentially moderates cerebrospinal fluid and plasma phosphorylated tau181 associations with multi-domain cognition

Neurobiol Aging. 2023 May:125:1-8. doi: 10.1016/j.neurobiolaging.2022.10.016. Epub 2023 Jan 18.

Abstract

Biofluid markers of phosphorylated tau181 (p-tau181) are increasingly popular for the detection of early Alzheimer's pathologic changes. However, the differential dynamics of cerebrospinal fluid (CSF) and plasma p-tau181 remain under investigation. We studied 727 participants from the Alzheimer's Disease Neuroimaging Initiative with plasma and CSF p-tau181 data, apolipoprotein (APOE) ε4 carrier status, amyloid positron emission tomography (PET) imaging, and neuropsychological data. Higher levels of plasma and CSF p-tau181 were observed among APOE ε4 carriers. CSF and plasma p-tau181 were significantly associated with memory, and this effect was greater in APOE ε4 carriers. However, whereas CSF p-tau181 was not significantly associated with language or attention/executive function among ε4 carriers or non-carriers, APOE ε4 status moderated the association of plasma p-tau181 with both language and attention/executive function. These findings lend support to the notion that p-tau181 biofluid markers are useful in measuring AD pathologic changes but also suggest that CSF and plasma p-tau181 have unique properties and dynamics that should be considered when using these markers in research and clinical practice.

Keywords: Apolipoprotein E; Cerebrospinal fluid; Cognition; Phosphorylated tau; Plasma.

Publication types

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

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoprotein E4* / cerebrospinal fluid
  • Apolipoprotein E4* / genetics
  • Biomarkers / cerebrospinal fluid
  • Cognition
  • Humans
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • tau Proteins
  • ApoE protein, human