2023 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)
The role of AD risk factor BIN1 on tau pathology in diabetes mouse models
What genetic risk factors contribute to tau tangle accumulation in Alzheimer’s?
Daniel Moreira-Silva, Ph.D.
University of South Florida
Tampa, FL - United States
Background
As obesity prevalence increases worldwide, there are also increases in the consequences for overall health related to obesity. Obesity is associated with an increased risk of type 2 diabetes which impacts multiple systems in the body, including the brain, and may increase one’s risk of developing Alzheimer’s. One of the hallmark brain changes associated with Alzheimer’s is the build-up (accumulation) of tau tangles. Studies have shown that diabetes increases the accumulation of tau tangles, one of the hallmark brain changes in Alzheimer’s. However, the mechanisms linking diabetes, tau tangles, and Alzheimer’s are unknown.
Dr. Daniel Moreira-Silva and colleagues believe that a specific gene called Bin1 which encodes the protein BIN1 and is a known risk factor for developing Alzheimer’s later in life, may also play a role in how diabetes increases one’s risk of Alzheimer’s.
Research Plan
Dr. Moreira-Silva and colleagues will use genetically engineered Alzheimer’s-like mice that also have diabetes to examine how loss of BIN1 impacts tau tangle accumulation and Alzheimer’s progression. They will do this by measuring the levels of tau tangles in the brains of these mice and performing cognitive and behavioral testing. The researchers will then examine what genes are turned “on” or “off” with loss of BIN1 to identify the potential mechanisms by which loss of BIN1 and diabetes contribute to Alzheimer’s.
Impact
The results from this study could improve our understanding of the mechanisms contributing to tau tangle accumulation in Alzheimer’s. The findings could also shed new light on how genetic risk factors contribute to Alzheimer’s progression.