2023 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)
Cerebrovascular Pathology Across the Alzheimer's Ccontinuum in Down syndrome
How may brain blood vessel damage impact the progression of Alzheimer’s disease in individuals with Down syndrome?
Lisi Flores Aguilar, Ph.D.
University of California, Irvine
Irvine, CA - United States
Background
Individuals with Down syndrome are at a high risk for developing Alzheimer’s. By the early age of 40, most individuals with Down syndrome have a build-up of beta-amyloid plaques and tau protein tangles in their brains, both hallmark brain changes observed in Alzheimer’s. Individuals with Down syndrome are also at high risk for another disease called cerebral amyloid angiopathy (CAA), which is closely related to Alzheimer’s. In CAA, beta-amyloid accumulates around the blood vessels, which can lead to stiffening of the vessels and problems with blood circulation. Recent studies have also found that in individuals with CAA, the perivascular spaces (or fluid-filled spaces around blood vessels) become enlarged and may indicate the presence of other disease-related damage.
In initial studies, Dr. Lisi Flores Aguilar and colleagues examined brains of individuals who had Down syndrome and Alzheimer’s. They found that brains with advanced Alzheimer’s showed significant damage to the blood brain barrier (BBB), a specialized structure that helps maintain a healthy brain environment by tightly regulating what goes into and out of the brain from circulating blood. Their results also indicated that BBB damage may be linked to enlarged perivascular spaces and CAA.
Research Plan
Dr. Flores Aguilar and colleagues will now perform a larger study of blood brain barrier damage in individuals with Down syndrome and Alzheimer’s. They will examine the brain tissue from 100 individuals who had Down syndrome and Alzheimer’s who died at different stages of life: (1) childhood, (2) young adulthood and (3) middle-age or older adulthood. First, they will assess how BBB damage occurs in the brain and how it may impact the health over time of brain cells and white matter (the brain’s “wiring system”). Next, they will examine how the development of enlarged perivascular spaces relates to BBB damage over time, as well as to other dementia-related brain changes, such as the clumping of beta-amyloid and tau protein.
Impact
The results of this project could shed new light on the biological mechanisms linking Alzheimer’s and CAA in individuals with Down syndrome. They could also promote the development of early-stage diagnostic methods and therapies for dementia in this population.