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2023 Alzheimer's Association Research Fellowship (AARF)

Synergistic contributions of APOE and vascular risk to cognitive decline

What factors contribute to brain blood vessel changes in Alzheimer’s?

Emily Rosenich, Ph.D.
Monash University
Clayton, Australia



Background

One of the hallmark brain changes in Alzheimer’s is the accumulation of beta-amyloid to form plaques. Beta-amyloid plaques can accumulate in and near the brain blood vessels – a condition known as cerebral amyloid angiopathy (CAA). CAA is associated with blood vessel stiffening and restricting blood flow into and throughout the brain. Studies have shown that vascular (blood vessel) disorders, such as high blood pressure and cardiovascular disease, may increase the risk of developing Alzheimer’s later in life. Yet, whether additional risk factors are associated with accumulation of amyloid plaques and developing CAA in Alzheimer’s are unknown. 

In initial studies, Dr. Emily Rosenich and colleagues found a potential link between vascular risk factors and a gene variation called APOE-e4, which has been shown, in certain populations, to increase one’s lifetime risk of developing Alzheimer’s. 

Research Plan

Building on their previous research, Dr. Rosenich will now work to  to understand the relationship between APOE-e4, vascular risk factors, and amyloid accumulation in Alzheimer’s. The team will use data from multiple ongoing studies to include over 500 individuals , with over one-third being APOE-e4 carriers, for the project. They will analyze APOE-e4 status, degree of vascular risk, and the level of amyloid plaque accumulation for each individual in the study and examine how each of these factors relate to one’s cognitive decline and Alzheimer’s risk.

Impact

The results of this project may help us understand the vascular contributions to Alzheimer’s and the role of APOE-e4 in this process. If successful, the findings may shed new light on new pathways that impact the risk of developing Alzheimer’s.

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