Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels

Yo El S. Ju, Sharon J. Ooms, Courtney Sutphen, Shannon L. Macauley, Margaret A. Zangrilli, Gina Jerome, Anne M. Fagan, Emmanuel Mignot, John M. Zempel, Jurgen A.H.R. Claassen, David M. Holtzman

Research output: Contribution to journalArticlepeer-review

431 Scopus citations

Abstract

Sleep deprivation increases amyloid-β, suggesting that chronically disrupted sleep may promote amyloid plaques and other downstream Alzheimer's disease pathologies including tauopathy or inflammation. To date, studies have not examined which aspect of sleep modulates amyloid-β or other Alzheimer's disease biomarkers. Seventeen healthy adults (age 35-65 years) without sleep disorders underwent 5-14 days of actigraphy, followed by slow wave activity disruption during polysomnogram, and cerebrospinal fluid collection the following morning for measurement of amyloid-β, tau, total protein, YKL-40, and hypocretin. Data were compared to an identical protocol, with a sham condition during polysomnogram. Specific disruption of slow wave activity correlated with an increase in amyloid-β 40 (r = 0.610, P = 0.009). This effect was specific for slow wave activity, and not for sleep duration or efficiency. This effect was also specific to amyloid-β, and not total protein, tau, YKL-40, or hypocretin. Additionally, worse home sleep quality, as measured by sleep efficiency by actigraphy in the six nights preceding lumbar punctures, was associated with higher tau (r = 0.543, P = 0.045). Slow wave activity disruption increases amyloid-β levels acutely, and poorer sleep quality over several days increases tau. These effects are specific to neuronally-derived proteins, which suggests they are likely driven by changes in neuronal activity during disrupted sleep.

Original languageEnglish
Pages (from-to)2104-2111
Number of pages8
JournalBrain
Volume140
Issue number8
DOIs
StatePublished - Aug 1 2017

Bibliographical note

Publisher Copyright:
© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

Keywords

  • EEG
  • beta-amyloid
  • sleep
  • slow wave activity
  • tau

ASJC Scopus subject areas

  • Clinical Neurology

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