The sleep-wake cycle affects the levels of a protein in our brain called tau, a new study in animals and humans shows. During periods of wakefulness, the protein accumulates in the brain fluid, the study's authors say, a problem exacerbated during periods of sleep deprivation. Thus, say the authors, optimization of the sleep-wake cycle should be an important treatment target to test in the prevention of Alzheimer disease (AD) and other so-called tauopathies. Tau, a protein in neurons, is released into brain interstitial fluid (ISF), where it can aggregate problematically in diseases like AD. What's more, once tau aggregation occurs in one region, it can spread to other brain regions. Tau is released by neuron signaling, which is greater during wakefulness. Previously, altered sleep patterns have been linked to increased levels of beta-amyloid. Here, the authors sought to study the impact of sleep-wake cycles on tau, which is more closely associated with neurodegeneration and is a key target for therapeutic intervention. Jerrah Holth and colleagues studied tau levels in the brain ISF of mice as their sleep patterns were disrupted. Tau levels increased 2-fold during the transition to the so-called dark period, when mice were awake 70% of the time, they say. The authors then sought to understand the impact of sleep deprivation on ISF tau. In an experiment with mice, sleep deprivation increased these levels significantly, they say. Next, using samples of cerebrospinal fluid they had previously collected from humans who were sleep-deprived, and in whom amyloid-beta was elevated, the authors found that levels of tau were similarly increased - even more so than amyloid-beta. Under longer sleep deprivation in mice, the spread of tau accelerated through the brain, they showed. Together, these and other results point to the sleep-wake cycle regulating both ISF tau in mice and CSF tau in humans.