Waste management deficiency in brain may contribute to cerebral amyloid angiopathy
By
Tony
LaRoche
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.
