IPA: TBI-induced Exosome Release Accelerates Alzheimer#s Disease Pathology

Project Number I01BX003643 Traumatic brain injury (TBI) resulting from combat is a prevalent head injury among Veterans. TBI can increase the risk of developing Alzheimer''s disease (AD) by 4-fold. AD is characterized by build-up of amyloid peptides forming plaques and hyper-phosphorylation of tau protein forming neurofibrillary tangles, a two-fold protein aggregation process leading to neurodegeneration and cognitive decline. It is not known how TBI increases the risk of developing AD and how to prevent TBI-induced AD. Our research showed that even mild TBI elicits shear forces in the brain that make particular cells secrete vesicles called exosomes. These TBI-induced exosomes bind to amyloid peptide and tau protein and enhance their neurotoxicity. Our goal is to interrupt TBI- induced exosome secretion to prevent or delay the onset of AD in Veterans.