New evidence for the involvement of sleep-related global brain activity in the elimination of Alzheimer’s-related brain debris

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Sleep Health | Sleep Review

Evidence of sleep-dependent, low-frequency (<0.1 Hz) global brain activity in the elimination of toxin formation associated with Alzheimer's disease is presented in a study published on June 1 in the open access journal PLOS Biology. The research was carried out by Xiao Liu, PhD, and colleagues at Pennsylvania State University. Neuronal activity was more closely related to CSF ​​flow in healthy controls than in higher risk groups and in patients, and the results could serve as a potential imaging marker for clinicians in evaluating patients.

It is believed that the development of Alzheimer’s disease is driven by the accumulation in the brain of the toxic proteins amyloid-β and tau. The glymphatic system of the brain plays a crucial role in the excretion of these toxins and previous work has shown a possible relationship between sleep-dependent global brain activity and the glymphatic system by showing that this activity is coupled by the flow of CSF.

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With 118 test subjects in the Alzheimer’s Disease Neuroimaging Initiative project, the researchers measured this global brain activity and CSF flow and looked at behavioral data. Subjects were given resting fMRI sessions two years apart, and the team compared their results with neurobiological and neuropsychological markers associated with Alzheimer’s disease.

The global brain signal in Alzheimer’s patients is associated with a weaker CSF flow compared to healthy controls. Feng Han and Xiao Liu at Pennsylvania State University

The strength of the association between brain activity and CSF flow was weaker in people at higher risk or who had Alzheimer’s disease. In addition, this weaker link was linked to higher amyloid-β levels and disease-related behavioral measures two years later. This suggests an important role for sleep-dependent global brain activity in clearing up brain debris, and its association with CSF flow could be useful as a future marker for clinical evaluation.

Liu said in a press release, “The study linked the link between global resting brain activity and CSF flow to the pathology of Alzheimer’s disease. The finding underscores the potential role of the low-frequency (<0.1 Hz) neuronal and physiological dynamics at rest in neurodegenerative diseases, presumably due to their sleep-dependent control of the CSF flow to wash out brain toxins. Future studies are warranted to fully understand global brain activity and related physiological modulations and their role in glymphatic clearance and neurodegenerative diseases. "

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