Study Uncovers How Traumatic Brain Injury May be Linked to Alzheimer’s Disease

Researchers used mouse models and human post-mortem brain tissue to assess the molecular underpinnings that may increase the risk of Alzheimer’s disease following traumatic brain injuries (TBI). The findings appeared in Acta Neuropathologica.

“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 via a press release.

This analysis showed that TBI increases hyperphosphorylated tau, astro- and microgliosis, synaptic dysfunction and cognitive impairments linked to developing Alzheimer’s disease. Moreover, the investigators 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 both mouse models and human post-mortem brain tissue with the history of TBI.

Ultimately, the analysis found that BAG3 overexpression ameliorates tau hyperphosphorylation, synaptic dysfunction, and cognitive deficits. “Based on our findings, we believe that targeting neuronal BAG3 may be a therapeutic strategy for preventing or reducing Alzheimer’s disease-like pathology,” said study first author Nicholas Sweeney, an Ohio State neuroscience research assistant.