An update on the association between traumatic brain injury and Alzheimer's disease: Focus on Tau pathology and synaptic dysfunction.

L.P. Li, J.W. Liang and H.J. Fu. An update on the association between traumatic brain injury and Alzheimer's disease: Focus on Tau pathology and synaptic dysfunction. NEUROSCI BIOBEHAV REVXXX-XXX,2020.-Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating conditions that have long-term consequences on individual's cognitive functions. Although TBI has been considered a risk factor for the development of AD, the link between TBI and AD is still in debate. Aggregation of hyperphosphorylated tau and intercorrelated synaptic dysfunction, two key pathological elements in both TBI and AD, play a pivotal role in mediating neurodegeneration and cognitive deficits, providing a mechanistic link between these two diseases. In the first part of this review, we analyze the experimental literatures on tau pathology in various TBI models and review the distribution, biological features and mechanisms of tau pathology following TBI with implications in AD pathogenesis. In the second part, we review evidences of TBI-mediated structural and functional impairments in synapses, with a focus on the overlapped mechanisms underlying synaptic abnormalities in both TBI and AD. Finally, future perspectives are proposed for uncovering the complex relationship between TBI and neurodegeneration, and developing potential therapeutic avenues for alleviating cognitive deficits after TBI.