2023 Alzheimer's Association Research Fellowship (AARF)
Role of amyloid angiopathy in AD-related perivascular protein accumulation
How is beta-amyloid in blood vessels related to other Alzheimer’s brain changes?
Valentina Perosa, M.D., Ph.D.
Massachusetts General Hospital
Boston, MA - United States
Background
A hallmark brain change associated with Alzheimer’s is the accumulation of the proteins tau and beta-amyloid into clumps called tangles and plaques, respectively. About half of the individuals with Alzheimer’s also have clumps of another protein, called TAR DNA-binding protein 43 (TDP-43), in their brains. Studies have shown that increases in TDP-43 may be connected to brain shrinkage (due to brain cell death) and accelerated cognitive decline in individuals with Alzheimer’s.
Beta-amyloid can accumulate near brain blood vessels and these accumulations are associated with increased stiffening of the vessels. When vessels are stiffer, it can be difficult for muscle cells in the blood vessels to properly pump blood, possibly restricting blood flow throughout the brain. This process is known as “cerebral amyloid angiopathy” or CAA. CAA is observed in about 80% of individuals with Alzheimer’s or a related dementia and has been shown to contribute to memory issues. It has been suggested that the inability to clear proteins along the blood vessels may worsen brain disease. However, how CAA and Alzheimer’s brain changes are connected is not well understood.
Research Plan
Dr. Valentina Perosa and colleagues aim to investigate the link between CAA and Alzheimer’s brain changes. The researchers will examine brain scans and tissue slices from individuals diagnosed with CAA and measure the amount of tau, beta-amyloid, and TDP-43 protein located around the blood vessels using advanced computational techniques. Using statistical methods, the researchers will then study the relationship between Alzheimer’s brain changes and CAA. Further, the researchers will take more detailed scans and tissue slices from brains with CAA to measure individual blood vessels in multiple brain regions crucial for memory function. They will create 3D images of individual blood vessels and look for tau and TDP-43 proteins to better understand how these Alzheimer’s-associated proteins relate to CAA.
Impact
The results of these studies will lead to a better understanding of the role of tau and TDP-43 in CAA, possibly leading to better diagnostic techniques and therapies.