Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer's disease

Sci Transl Med. 2019 Jan 9;11(474):eaau6550. doi: 10.1126/scitranslmed.aau6550.


In Alzheimer's disease (AD), deposition of insoluble amyloid-β (Aβ) is followed by intracellular aggregation of tau in the neocortex and subsequent neuronal cell loss, synaptic loss, brain atrophy, and cognitive impairment. By the time even the earliest clinical symptoms are detectable, Aβ accumulation is close to reaching its peak and neocortical tau pathology is frequently already present. The period in which AD pathology is accumulating in the absence of cognitive symptoms represents a clinically relevant time window for therapeutic intervention. Sleep is increasingly recognized as a potential marker for AD pathology and future risk of cognitive impairment. Previous studies in animal models and humans have associated decreased non-rapid eye movement (NREM) sleep slow wave activity (SWA) with Aβ deposition. In this study, we analyzed cognitive performance, brain imaging, and cerebrospinal fluid (CSF) AD biomarkers in participants enrolled in longitudinal studies of aging. In addition, we monitored their sleep using a single-channel electroencephalography (EEG) device worn on the forehead. After adjusting for multiple covariates such as age and sex, we found that NREM SWA showed an inverse relationship with AD pathology, particularly tauopathy, and that this association was most evident at the lowest frequencies of NREM SWA. Given that our study participants were predominantly cognitively normal, this suggested that changes in NREM SWA, especially at 1 to 2 Hz, might be able to discriminate tau pathology and cognitive impairment either before or at the earliest stages of symptomatic AD.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology*
  • Amyloid / metabolism
  • Amyloid beta-Peptides / metabolism
  • Eye Movements / physiology*
  • Female
  • Humans
  • Male
  • Positron-Emission Tomography
  • Sleep / physiology*
  • Sleep, Slow-Wave
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / metabolism*


  • Amyloid
  • Amyloid beta-Peptides
  • tau Proteins