2023 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)
The link between axon damage in traumatic brain injury and tau pathogenesis
How do brain injuries contribute to tau build-up in the brain?
Hailong Song, Ph.D.
University of Pennsylvania
Philadelphia, PA - United States
Background
Traumatic brain injury (TBI) results from an injury to the head that disrupts normal brain function. Studies have shown that TBI may increase a individual’s risk for developing brain diseases, including Alzheimer’s and other dementia, later in life. After a TBI, the brain develops clumps of a protein called tau which form aggregates called tau tangles, one of the hallmark brain changes in Alzheimer’s. However, the mechanisms by which TBI leads to tau accumulation and increases Alzheimer’s risk are unknown.
Dr. Hailong Song and colleagues have initial evidence to suggest that axons, the long, armlike structures on nerve cells that help transport nutrients and other components along nerve cells, may play a role.
Research Plan
Building on their initial findings, Dr. Song and team will examine how axon damage contributes to tau build-up and potentially increases one’s risk of developing Alzheimer’s after a TBI. They will do this using a type of stem cell called iPSCs (induced Pluripotent Stem Cells) which can be grown in a laboratory dish and can be programmed into any type of cell in the body to make nerve cells. They will also use a special technique developed by the researchers that mimics axon damage after a TBI in cells grown in a laboratory dish. The team will measure tau build-up in axons after a “TBI” in the cells. Next, the researchers will measure the levels of tau build-up and associate them with axon damage in brain tissue from individuals who had a TBI and individuals who had Alzheimer’s.
Impact
The results of this study may shed new light on the mechanisms by which TBI and tau accumulation are linked. If successful, it could also identify new potential strategies for preventing Alzheimer’s in individuals who experience a TBI.