Weaker association between brain activity and cerebrospinal fluid flow increases the likelihood of Alzheimer's disease

New imaging research shows that low-frequency brain activity during sleep was less connected with cerebrospinal fluid flow in patients with Alzheimer's disease due to toxin buildup.

Alzheimers Disease

Alzheimer's Disease. Image Credit: LightField Studios/Shutterstock.com

Connections between Alzheimer's disease and brain activity

Alzheimer's disease is a neurodegenerative disease believed to originate from an accumulation of the toxic amyloid-βand tau proteins in the brain. Symptoms include a range of speaking, learning, and memory-related deficiencies and are also the cause of up to 70% of cases of dementia.

To counteract the buildup of harmful proteins, the brain’s glymphatic system clears up such toxins, and thus serves a key function in preventing neural damage or the onset of neurodegenerative diseases. Previous findings have also demonstrated a relationship between sleep-dependent global brain activity and the glymphatic system, a waste disposal system of the central nervous system that is most active during sleep-related low-frequency brain activity.

Scientists have therefore attempted to better understand this relationship, including what factors may contribute to negatively affecting this relationship, and what would the outcomes be for a reduced connection between glymphatic system activity and cerebrospinal fluid flow.

A weaker connection in susceptible individuals

In a new study published in PLOS Biology by Xiao Liu and colleagues at The Pennsylvania State University, researchers used 118 subjects in the Alzheimer's Disease Neuroimaging Initiative project to further investigate the nature of the relationship between Alzheimer's Disease and the glymphatic system.

Brain activity and cerebrospinal fluid flow were measured across all subjects during two fMRI sessions that were two years apart, and researchers also incorporated behavioral data to eliminate potential confounding factors. Researchers used a combination of neurobiological and neuropsychological markers related to Alzheimer's disease, such as concentrations of the toxic protein amyloid-β, to further determine the severity of the disease in each subject.

Data analysis revealed that the strength of the connection between brain activity and cerebrospinal fluid flow was weaker in individuals at a higher risk or who had already developed Alzheimer's disease.

Moreover, this weaker relationship was further associated with higher levels of amyloid-β and behavioral measures related to increased disease risk. Altogether, results suggest that sleep-dependent global brain activity is key in the clearance of brain waste.

The study linked the coupling between the resting-state global brain activity and cerebrospinal fluid flow to Alzheimer's disease pathology. The finding highlights the potential role of low-frequency (<0.1 Hz) resting-state neural and physiological dynamics in neurodegenerative diseases, presumably due to their sleep-dependent driving of cerebrospinal fluid flow to wash out brain toxins.”

Dr. Liu

Future research and the potential as an imaging marker for clinicians

This study further demonstrates the complex associations between brain activity and functioning across cerebral parts. Future research could aim to determine whether similar relationships exist in other pathways, as well as consider the use of the connection between slow-wave activity and cerebrospinal fluid flow as an imaging marker for clinical evaluations.

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

The potential diagnostic capability of this association will provide key information on identifying patients at risk. Findings from this study may be extended to other diseases. Indeed, other neurodegenerative diseases may demonstrate similar weaker connections or dysfunctional brain-related associations, including Parkinson's and Huntington’s diseases, which remain the most common neurodegenerative disorders and affect millions of people around the world.

  • Han F, Chen J, Belkin-Rosen A, Gu Y, Luo L, Buxton OM, et al. (2021) Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease-related pathology. PLoS Biol 19(6): e3001233. https://doi.org/10.1371/journal.pbio.3001233
James Ducker

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James Ducker

James completed his bachelor in Science studying Zoology at the University of Manchester, with his undergraduate work culminating in the study of the physiological impacts of ocean warming and hypoxia on catsharks. He then pursued a Masters in Research (MRes) in Marine Biology at the University of Plymouth focusing on the urbanization of coastlines and its consequences for biodiversity.  


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