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Sunday, March 27, 2022

Clean out the brain gunk

Waste management deficiency in brain may contribute to cerebral amyloid angiopathy

By Tony LaRoche

A healthy brain requires regular “clearing” to flush away toxins and other waste products that can lead to dementia and cognitive impairments. 

But a new study published in Nature Aging and conducted by a team of researchers at the University of Rhode Island, Yale School of Medicine, and Stony Brook University shows that trouble with the brain’s clearance systems may contribute to cerebral amyloid angiopathy (CAA), a condition in older adults that causes brain hemorrhages and commonly occurs with Alzheimer’s disease.  

William Van Nostrand, Herrmann Professor of Neuroscience and co-director of the George & Anne Ryan Institute at URI, was a co-senior author on the study, which found that both the glymphatic system and lymphatic drainage were impaired in a rodent model of cerebral amyloid angiopathy. 

“An active, healthy clearance system prevents the build-up of waste products, such as the amyloid-beta protein that accumulates in CAA and Alzheimer’s disease,” said Van Nostrand. “We saw in our CAA models that these systems had deteriorated, so the brain gets backed-up with waste.” 

Using an innovative magnetic resonance imaging (MRI) technique developed by Helene Benveniste, professor of anesthesiology at Yale School of Medicine, and computational fluid dynamics implemented by Allen Tannenbaum, distinguished professor of computer science and applied mathematics and statistics at Stony Brook University, the team observed that when cerebral amyloid angiopathy  was present, cerebral spinal fluid failed to flush waste and by-products through the normal glymphatic channels. They also saw that lymphatic drainage, another process essential to clearing waste from the brain, was impaired. 

“When these clearance systems aren’t working, it creates a vicious cycle,” said Van Nostrand. “The increasing build-up of waste leads to more trouble clearing, which leads to more build-up.”

The build-up of amyloid-beta deposits in the brain blood vessels is one of the hallmarks of cerebral amyloid angiopathy and Alzheimer’s disease. While it is not yet understood why the brain’s clearance systems may become dysfunctional, this breakdown provides another clue into a potential target for treating both diseases.

“If we can find ways to preserve or increase glymphatic clearance this could aid in preventing or decreasing accumulation of amyloid-beta and other noxious substances from brain that contribute to CAA and Alzheimer’s disease,” said Van Nostrand. 

The co-first authors of the study are Xinan Chen of Stony Brook University and Xiaodan Liu of Yale University. Co-authors are Sunil Koundal and Feng Dai of Yale University; Rena Elkin of Memorial Sloan Kettering Cancer Center; Xiaoyue Zhuand Feng Xu of URI; Brittany Monte, Maysam Pedram, and Hedok Lee of Stony Brook University; and Jonathan Kipnis of Washington University. 

The research was supported by a grant from the National Institutes of Health’s National Institute on Aging and the Cure Alzheimer’s Fund.