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2014 Grants - Stein
Genetic Risk Factors Underlying Chronic Trauma and Alzheimer’s Pathology
Thor Stein, Ph.D.
Bedford VA Research Corporation, Inc.
2014 New Investigator Research Grant
Alzheimer’s disease and chronic traumatic encephalopathy (CTE) are progressive brain disorders, and head trauma is a risk factor for both. CTE typically develops after repeated physical brain insults called mild traumatic brain injuries (TBIs) — which often involve a temporary loss of consciousness or memory. As with Alzheimer’s, CTE hallmarks include personality and behavioral changes, declines in cognition and permanent memory loss. Moreover, both Alzheimer’s and CTE involve the accumulation of abnormal tau protein in the brain; accumulations that can contribute to a decrease in the ability of brain cells to function properly and communicate with one another. Yet unlike Alzheimer’s, as of yet, there are no known genetic risk factors for the development of CTE.
Thor Stein, Ph.D., and colleagues are studying the possible role of genetic risk factors in CTE. For this effort, they have used data from a large group of people who had CTE or CTE with Alzheimer’s. They found that a natural gene variation called APOE- ɛ4, which is known to increase an individual’s risk for Alzheimer’s disease, is also expressed in people with CTE. In addition, CTE brains express genes for abnormal tau that differ from those linked to Alzheimer’s.
For their current effort, Dr. Stein and colleagues will conduct a larger analysis of their Alzheimer’s/CTE data using novel genetic analysis techniques to better clarify the role of APOE- ɛ4 and tau-related genes in the development of CTE and/or Alzheimer’s disease. They also plan to analyze areas of the brain that are affected by early-stage CTE — and examine how the expression patterns of APOE- ɛ4 and abnormal tau genes change over time as CTE and Alzheimer’s progress. These studies will increase the understanding of how brain trauma contributes to the development or acceleration of brain changes associated with Alzheimer’s disease. In addition, these efforts could lead to novel procedures for diagnosing and treating both disorders.