Australasian Science: Australia's authority on science since 1938

Possible Link Between Sleep and Alzheimer’s Disease

Genetic variations in a protein that removes toxins from the brain while we sleep not only reduce sleep quality but has been associated with a build-up of beta-amyloid — the main component of amyloid plaques found in the brains of patients with Alzheimer’s disease.

The study, published in Translational Psychiatry ( and led by A/Prof Simon Laws and Dr Stephanie Rainey-Smith of Edith Cowan University, focused on Aquaporin-4 (AQP4) due to its role in our brain’s night-time “housekeeping” system.

“Previously, it was thought that sleep problems were simply a characteristic of Alzheimer’s disease, but more recent studies have shown that a bidirectional relationship exists, with poor sleep also contributing to higher amyloid levels,” Laws said.

One suggested mechanism the brain uses to remove beta-amyloid is the glymphatic system, which flushes out toxins during sleep. Laws said a key component of this system is AQP4, which is a water-channel protein that acts like tiny drains through which toxins are flushed.

“For the first time, we’ve found that people with genetic variants in AQP4 who also have problems getting to sleep and sleep for shorter periods have high levels of beta-amyloid in the brain,” Laws said. “This adds strong evidence to the idea that the glymphatic system is vital, and suggests that genetic variants in AQP4 may lead to a poorly functioning glymphatic system.”

Good sleep is vital, as the glymphatic system shuts down during waking hours. As such, poor sleep or other factors that result in impaired functioning of the glymphatic system allow beta-amyloid to build up in the brain over time.

“In some individuals, their glymphatic system may function perfectly well on six or eight hours sleep, but this study suggests that individuals with a genetic variation might need more sleep,” Laws said.

While more research is required, these new findings could lead to individualised treatments for people with poor sleep quality. The challenge will be to help people sleep longer or better, which could then compensate for a glymphatic system that functions poorly due to genetic variation.

“Approaches that may help achieve this could include modifying a person’s sleeping environment, such that noise and light is kept to a minimum,” Laws said.