National Library of Medicine - National Center for Biotechnology Information

2019 Aug 7;39(32):6315-6324. doi: 10.1523/JNEUROSCI.0503-19.2019. Epub 2019 Jun 17.

Sleep as a Potential Biomarker of Tau and β-Amyloid Burden in the Human Brain

Joseph R Winer 1, Bryce A Mander 2 3, Randolph F Helfrich 4, Anne Maass 4 5, Theresa M Harrison 4, Suzanne L Baker 6, Robert T Knight 4, William J Jagust 4 6, Matthew P Walker 1 4

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Abstract

Recent proposals suggest that sleep may be a factor associated with accumulation of two core pathological features of Alzheimer's disease (AD): tau and β-amyloid (Aβ). Here we combined PET measures of Aβ and tau, electroencephalogram sleep recordings, and retrospective sleep evaluations to investigate the potential utility of sleep measures in predicting in vivo AD pathology in male and female older adults. Regression analyses revealed that the severity of impaired slow oscillation-sleep spindle coupling predicted greater medial temporal lobe tau burden. Aβ burden was not associated with coupling impairment but instead predicted the diminished amplitude of <1 Hz slow-wave-activity, results that were statistically dissociable from each other. Additionally, comparisons of AD pathology and retrospective, self-reported changes in sleep duration demonstrated that changes in sleep across the lifespan can predict late-life Aβ and tau burden. Thus, quantitative and qualitative features of human sleep represent potential noninvasive, cost-effective, and scalable biomarkers (current and future forecasting) of AD pathology, and carry both therapeutic and public health implications.SIGNIFICANCE STATEMENT Several studies have linked sleep disruption to the progression of Alzheimer's disease (AD). Tau and β-amyloid (Aβ), the primary pathological features of AD, are associated with both objective and subjective changes in sleep. However, it remains unknown whether late life tau and Aβ burden are associated with distinct impairments in sleep physiology or changes in sleep across the lifespan. Using polysomnography, retrospective questionnaires, and tau- and Aβ-specific PET, the present study reveals human sleep signatures that dissociably predict levels of brain tau and Aβ in older adults. These results suggest that a night of polysomnography may aid in evaluating tau and Aβ burden, and that treating sleep deficiencies within decade-specific time windows may serve in delaying AD progression.

Keywords: Alzheimer's disease; PET; aging; beta-amyloid; sleep; tau.

Copyright © 2019 the authors.

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Figures

Figure 1.

Figure 1. Mean PET binding demonstrates tau…

 

Figure 2.

Figure 2. Associations between SO-spindle coupling, tau,…

 

Figure 3.

Figure 3. Associations between NREM SWA, tau,…

 

Figure 4.

Figure 4. Associations between retrospective change in…

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Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
    Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / analysis*
  • Aniline Compounds
    Biomarkers
    Carbolines
  • Carbon Radioisotopes
    Electroencephalography
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Models, Neurological
  • Nerve Tissue Proteins / analysis*
  • Polysomnography
  • Positron-Emission Tomography
  • Predictive Value of Tests
  • Prognosis
  • Radiopharmaceuticals
  • Sleep Disorders, Intrinsic / diagnostic imaging
  • Sleep Disorders, Intrinsic / metabolism*
  • Sleep Disorders, Intrinsic / pathology
  • Sleep Stages / physiology*
  • Temporal Lobe / chemistry*
  • Thiazoles
  • tau Proteins / analysis*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Biomarkers
  • Carbolines
  • Carbon Radioisotopes
  • Carbon-11
    Fluorine Radioisotopes
  • MAPT protein, human
  • Nerve Tissue Proteins
  • Radiopharmaceuticals
  • Thiazoles
  • tau Proteins
  • Fluorine-18
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

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