BAG3 attenuates tau hyperphosphorylation and gliosis induced by traumatic brain injury

Alzheimer disease (AD) and traumatic brain injury (TBI) are two devastating brain disorders with complex relationships. Growing evidence supports that early or middle life of TBI may be a risk factor for developing late‐life AD and AD‐related dementias (ADRD). Tau hyperphosphorylation and gliosis may serve as a causative link between TBI and AD as well as ADRD. We have recently identified BCL2 associated athanogene 3 (BAG3) as a hub gene of regulating tau protein homeostasis. The protein level of BAG3 is significantly reduced in neurons, but it is increased in astrocytes of human AD compared to controls. We hypothesized that overexpression of BAG3 in neurons would attenuate tau hyperphosphorylation and gliosis induced by TBI.