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

Abstract

IntroductionSleep deprivation increases cerebrospinal fluid (CSF) amyloid beta (A beta) and tau levels; however, sleep's effect on A beta and tau in plasma is unknown. MethodsIn a cross-over design, CSF A beta 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. ResultsA beta 40, A beta 42, unphosphorylated tau threonine181 (T181), unphosphorylated tau threonine-217 (T217), and phosphorylated T181 (pT181) concentrations increased similar to 35% to 55% in CSF and decreased similar to 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 A beta 42/40, pT181/T181, and pT181/A beta 42 ratios were stable longitudinally in both groups. DiscussionThese 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.