Acute sleep loss decreases CSF-to-blood clearance of Alzheimer's disease biomarkers

Alzheimers Dement. 2023 Jul;19(7):3055-3064. doi: 10.1002/alz.12930. Epub 2023 Jan 25.

Abstract

Introduction: Sleep deprivation increases cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels; however, sleep's effect on Aβ and tau in plasma is unknown.

Methods: In a cross-over design, CSF Aβ and tau concentrations were measured in five cognitively normal individuals who had blood and CSF collected every 2 hours for 36 hours during sleep-deprived and normal sleep control conditions.

Results: Aβ40, Aβ42, unphosphorylated tau threonine181 (T181), unphosphorylated tau threonine-217 (T217), and phosphorylated T181 (pT181) concentrations increased ∼35% to 55% in CSF and decreased ∼5% to 15% in plasma during sleep deprivation. CSF/plasma ratios of all Alzheimer's disease (AD) biomarkers increased during sleep deprivation while the CSF/plasma albumin ratio, a measure of blood-CSF barrier permeability, decreased. CSF and plasma Aβ42/40, pT181/T181, and pT181/Aβ42 ratios were stable longitudinally in both groups.

Discussion: These findings show that sleep loss alters some plasma AD biomarkers by lowering brain clearance mechanisms and needs to be taken into account when interpreting individual plasma AD biomarkers but not ratios.

Keywords: Alzheimer's disease; biomarkers; sleep.

Publication types

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

MeSH terms

  • Alzheimer Disease* / cerebrospinal fluid
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Humans
  • Peptide Fragments / cerebrospinal fluid
  • Sleep
  • Sleep Deprivation
  • Sleep Initiation and Maintenance Disorders*
  • Sleep Wake Disorders*
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • tau Proteins
  • Biomarkers
  • Peptide Fragments