Each year, about 2.5 million people suffer from traumatic brain injuries (TBI), which often increases their risk for developing Alzheimer's disease later in life. Researchers led by The Ohio State University Wexner Medical Center and College of Medicine used mouse models and human post-mortem brain tissue to study the molecular underpinnings that may increase the risk of Alzheimer's after TBI.
"Because of the prevalence of both TBI and Alzheimer's in humans, understanding the molecular mechanism that underlies the transition from TBI to Alzheimer's is vital to developing future therapies that reduce this risk," said study senior author Hongjun "Harry" Fu, PhD, assistant professor of neuroscience at Ohio State. Study findings are published online in the journal Acta Neuropathologica . Researchers found that TBI increases hyperphosphorylated tau, astro- and microgliosis, synaptic dysfunction and cognitive impairments linked to developing Alzheimer's disease.
Furthermore, they found that downregulation of BAG3, a protein involved in protein clearance through the autophagy-lysosome pathway, contributes to the accumulation of hyperphosphorylated tau in neurons and oligodendrocytes after TBI in the mouse models and human post-mortem brain tissue with the history of TBI. Using an AAV-based approach of overexpressing BAG3 in neurons, they found that BAG3 overexpression ameliorates tau hyperphosphorylation, synaptic dysfunction, and cognitive deficits, likely through the enhancement o.
