Neuroinflammation and Tau Interact with Amyloid in Predicting Sleep Problems in Aging Independently of Atrophy

Cereb Cortex. 2018 Aug 1;28(8):2775-2785. doi: 10.1093/cercor/bhx157.


Sleep problems relate to brain changes in aging and disease, but the mechanisms are unknown. Studies suggest a relationship between β-amyloid (Aβ) accumulation and sleep, which is likely augmented by interactions with multiple variables. Here, we tested how different cerebrospinal fluid (CSF) biomarkers for brain pathophysiology, brain atrophy, memory function, and depressive symptoms predicted self-reported sleep patterns in 91 cognitively healthy older adults over a 3-year period. The results showed that CSF levels of total- and phosphorylated (P) tau, and YKL-40-a marker of neuroinflammation/astroglial activation-predicted poor sleep in Aβ positive older adults. Interestingly, although brain atrophy was strongly predictive of poor sleep, the relationships between CSF biomarkers and sleep were completely independent of atrophy. A joint analysis showed that unique variance in sleep was explained by P-tau and the P-tau × Aβ interaction, memory function, depressive symptoms, and brain atrophy. The results demonstrate that sleep relates to a range of different pathophysiological processes, underscoring the importance of understanding its impact on neurocognitive changes in aging and people with increased risk of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / cerebrospinal fluid*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Apolipoproteins E / genetics
  • Atrophy / cerebrospinal fluid
  • Atrophy / pathology
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid
  • Encephalitis / cerebrospinal fluid*
  • Encephalitis / diagnostic imaging
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Neurofilament Proteins / cerebrospinal fluid
  • Sleep Wake Disorders / cerebrospinal fluid*
  • Sleep Wake Disorders / diagnostic imaging
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Apolipoproteins E
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins