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Researchers investigate links between deep sleep and Alzheimer’s-related proteins. Retno Ayu Adiati/EyeEm/Getty Images
  • A new study links sleep-dependent brain activity with the excretion of toxic proteins related to Alzheimer’s disease.
  • This activity is weaker in the brains of people with a higher risk of cognitive decline.
  • The discovery could provide a potential biomarker in diagnosing neurodegenerative diseases.

Research published in PLOS Biology suggests that global brain activity during deep sleep decreases Alzheimer’s-related toxin buildup.

It upholds previous findings indicating that low frequency brain waves produced during the non-rapid eye movement (NREM) sleep phase can play a vital role in clearing brain waste.

Dr. Xiao Liu, assistant professor of biomedical engineering at the Pennsylvania State University, led the study.

Alzheimer’s disease develops in line with increased levels of the proteins amyloid-β (Aβ) and tau in the brain. Extensive research implicates these substances as major contributors to cognitive deterioration.

By the time symptoms of Alzheimer’s disease manifest, the toxic buildup has advanced dramatically. This accumulation could begin 10–20 years before the onset of dementia symptoms.

Experts believe that cerebrospinal fluid (CSF) carries such waste products away from the brain through the glymphatic system, which is a system of channels in the central nervous system.

Glial cells, which make up a substantial amount of the brain’s total mass, work with blood vessels to help shield neurons from physical and chemical damage.

According to a 2021 review, impairments in glymphatic draining might lead to an extracellular buildup of waste products in the brain.

This could breed unfavorable conditions in the central nervous system, leading to neurodegenerative diseases, such as Alzheimer’s disease.

Growing bodies of research suggest that deep sleep may help the brain wash away Alzheimer’s-related toxins.

At the NREM stage, the brain’s slow, steady electrical waves act as a cleaning mechanism.

A 2019 review notes that large low frequency brain waves occur just before a pulse of CSF floods through the brain. The study reports that these “oscillations in neural activity support memory consolidation and neuronal computation.”

These flows of fluid occur on a significantly broader scale during deep rest than during wakefulness.

To investigate this further, Dr. Liu and his colleagues studied 118 subjects from the Alzheimer’s Disease Neuroimaging Initiative. The participants comprised “7 [patients with Alzheimer’s disease], 62 [patients with mild cognitive impairment], 18 significant memory concern […] patients, and 31 healthy controls.”

The participants underwent resting-state functional MRI sessions 2 years apart.

The scientists probed into global brain activity and CSF flow in addition to behavioral data. They compared their assessments with Alzheimer’s-associated markers, including CSF flow, Aβ levels, and behaviors.

The participants with a higher risk of Alzheimer’s disease and those who had already developed the condition exhibited a weaker connection between brain activity and CSF flow.

This defective connection also correlated with higher Aβ levels and Alzheimer’s-related behavioral patterns after 2 years.

Dr. Liu said: “The study linked the coupling between the resting-state global brain activity and [CSF] flow to Alzheimer’s disease pathology. The finding highlights the potential role of low frequency (less than 0.1 [hertz]) resting-state neural and physiological dynamics in the neurodegenerative diseases, presumably due to their sleep-dependent driving of [CSF] flow to wash out brain toxins.”

The coupling was noticeably weaker in female and older participants, who have a higher risk of developing Alzheimer’s disease.

The current study agrees with earlier studies that link sleep with Alzheimer’s disease progression. In 2018, a group of researchers found that just 1 night of sleep deprivation increases the Aβ burden in the brain.

In a 2019 clinical trial involving cognitively healthy individuals, NREM sleep negatively correlated with Aβ deposits and tau protein clumping in several brain regions. The authors recommended that sleep analysis could be helpful in detecting Alzheimer’s disease.

However, the current study does have certain limitations. For instance, it involved a limited sample size and a relatively short time frame. Moreover, its authors maintain that its results cannot prove a causal relationship.

Dr. Liu concluded: “Future studies are warranted to fully understand the global brain activity and associated physiological modulations and their role in glymphatic clearance and neurodegenerative diseases.”

This analysis further highlights how deeply sleep quality can impact brain health. Sleep activity could prove to be a revealing marker for risk of cognitive decline, increasing the chances of early intervention.

Medical News Today asked Dr. Arthur Toga, a neuroscientist at the University of California’s Keck School of Medicine in Los Angeles, about the significance of this study. He commented:

“This work is an important contribution to our understanding of the mechanisms involved in clearing toxins from the brain. There are several mechanisms that may contribute, including dysregulation of the blood-brain barrier and changes in the glymphatic system. […] The roles of sleep, the glymphatic system, CSF, and perivascular spaces in the clearance of amyloid and tau are not fully understood, and this paper brings us one step closer.”