Accumulation of tau hinders the brain’s ability to function during sleep

The team led by Omer Sharon and Matthew Walker discovered a link between the accumulation of tau protein in the frontal cortex of the brain, disruption of specific slow waves during deep (slow‑wave, non‑REM) sleep, and impaired formation of long‑term memories. Tau is a protein known as a marker of Alzheimer’s disease development; its excess disrupts the normal functioning of neurons.

During deep sleep, slow, synchronized waves of electrical activity spread through the brain; they originate in the frontal cortex and spread across large areas of the brain. Each such wave reflects the simultaneous shutdown and subsequent activation of huge groups of neurons. For memory consolidation, it is critically important that these waves cascade, covering large areas. It is precisely this coordinated activity, according to researchers, that partly explains why we need sleep.

As people age, tau accumulates in the brain of many people. Because of this, slow waves become less synchronous, travel over shorter distances, and increasingly occur in isolation; experts have figuratively called them “lonely waves.” Such changes prevent the brain from effectively storing daytime impressions in long‑term memory.

To trace this connection, researchers used several methods at once. Using electroencephalography (EEG), they compared the pattern of slow waves in young people (about 20 years old) and older adults (60–70 years old). In young people, the waves “traveled” across the brain over a distance of about the width of a palm, while in older adults they became shorter and more fragmented. At the same time, using positron emission tomography (PET), scientists monitored the accumulation of tau in the frontal cortex. It turned out that the more protein there was, the more severely the coordination of the waves was disrupted, and the worse people were at remembering word associations learned before going to sleep.

It is important that these impairments were detected in people without a diagnosis of Alzheimer’s disease; in them, tau was present at a subclinical level, and the memory decline was within the age‑related norms. Upon a follow‑up examination several years later, those whose tau levels had increased simultaneously showed deteriorating coherence of slow waves and a reduced ability to retain memories after a night’s sleep.

For additional verification, tau levels in the cerebrospinal fluid were measured in another group of elderly people. Although this method did not allow for precise localization of tau in the frontal lobe, the pattern turned out to be similar. In people with more disorganized slow waves, the ratio of tau to another protein associated with Alzheimer’s disease (amyloid) was higher. The fact that two different approaches yielded consistent results makes the study’s conclusions particularly convincing.

Memory decline is a complex process in which local pathology in the frontal regions (where global waves originate) and the quality of deep sleep play an important role. At the same time, it is still impossible to say what comes first: tau accumulation causes the breakdown of waves, or sleep disruption accelerates protein accumulation. The answer to this question will determine which interventions should be developed to prevent cognitive impairments.

Thus, slow waves of deep sleep can serve as a kind of biomarker: their characteristics reflect not only the quality of sleep but also hidden changes in the brain associated with the risk of Alzheimer’s disease. Understanding this connection may help open up new opportunities for early detection of people at risk and for finding ways to support memory health.