Poor sleep is a symptom of Alzheimer’s disease (AD) that worsens as the disease progresses and is also suggested to be an early symptom of AD. It has been known for some time that amyloid-β (Aβ), which aggregates in the plaques and tangles that are the neuropathologic hallmark of the disease, fluctuates with the sleep-wake cycle. A single night of sleep deprivation has been correlated with a 30% increase in the levels of Aβ in research subjects’ cerebrospinal fluid (CSF).
Now, in studies published in Science and Science Translational Medicine, it has been shown that levels of tau also fluctuate with the sleep-wake cycle and correlate with the amount of slow-wave nonREM sleep. Sleep deprivation in human subjects correlated with approximately a 50% increase in levels of tau in subjects’ CSF samples; in a mouse model of AD, they found sleep deprivation doubled tau levels in interstitial fluid samples. In the mouse model, sleep deprivation also correlated with inceased spread of tau tangles. Chemogenetically-driven wakefulness in mice also significantly increased both Aβ and tau.
Using single-channel EEG, researchers from the same group found that AD pathology measured by PET scan, particularly tauopathy, correlated inversely with slow-wave activity during nonREM sleep, suggesting that the quality of sleep is also an important factor that relates to tau aggregation. The authors of these papers concluded that tau pathology is regulated by sleep-wake cycles and also suggested that measures of slow-wave activity of nonREM sleep could serve as a diagnostic biomarker.
Hans D. Katzberg, MD, MSc, FRCPC; and Hamid Sadeghian, MD, FRCPC
Georgette A. Khoury, MSN, APRN-BC; and Ira J. Goodman, MD
Jonathan R. Brent, MD, PhD; and Senda Ajroud-Driss, MD