@article{47953f141e924f469466a124d6d635bf,
title = "Acute sleep loss decreases CSF-to-blood clearance of Alzheimer's disease biomarkers",
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",
author = "Haiyan Liu and Barth{\'e}lemy, {Nicolas R.} and Vitaliy Ovod and Bollinger, {James G.} and Yingxin He and Chahin, {Samir L.} and Brendan Androff and Bateman, {Randall J.} and Lucey, {Brendan P.}",
note = "Funding Information: The authors thank the participants for their time and commitment to the study. The authors thank Dr. Donald Elbert for helpful discussion. This study was funded by the Centene Corporation contract (P19-00559) for the Washington University-Centene ARCH Personalized Medicine Initiative. Additional support was provided by the National Institutes of Health (NIH): R03 AG047999, K76 AG054863, P50 AG05681, and P01 AG26276 (National Institute on Aging); R01 NS065667 and R01 NS097799 (National Institute of Neurological Disorders and Stroke). The 15N-441 tau internal standard was a generous gift from G. Lippens. Dr. N. Kanaan generously provided the Tau1 antibody that is a tau epitope 192-199. HJ8.5 antibody to tau epitope 27-35 was generously given by Dr. David Holtzman. The funding sources had no role in the study design, data collection, management, analysis, interpretation of the data, or manuscript preparation. Funding Information: The authors thank the participants for their time and commitment to the study. The authors thank Dr. Donald Elbert for helpful discussion. This study was funded by the Centene Corporation contract (P19‐00559) for the Washington University‐Centene ARCH Personalized Medicine Initiative. Additional support was provided by the National Institutes of Health (NIH): R03 AG047999, K76 AG054863, P50 AG05681, and P01 AG26276 (National Institute on Aging); R01 NS065667 and R01 NS097799 (National Institute of Neurological Disorders and Stroke). The 15N‐441 tau internal standard was a generous gift from G. Lippens. Dr. N. Kanaan generously provided the Tau1 antibody that is a tau epitope 192‐199. HJ8.5 antibody to tau epitope 27‐35 was generously given by Dr. David Holtzman. The funding sources had no role in the study design, data collection, management, analysis, interpretation of the data, or manuscript preparation. Publisher Copyright: {\textcopyright} 2023 the Alzheimer's Association.",
year = "2023",
month = jul,
doi = "10.1002/alz.12930",
language = "English",
volume = "19",
pages = "3055--3064",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
number = "7",
}