ApoE4-associated phospholipid dysregulation contributes to development of Tau hyper-phosphorylation after traumatic brain injury.

ABSTRACT: The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP₂) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP₂ degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP₂ levels in ApoE4 mice did not increase after blast TBI. Following blast TBI, phospho-Tau (pTau) levels were unchanged in ApoE3 mice, whereas in ApoE4 mice, levels of pTau were significantly increased. To determine the causal relationship between changes in pTau and PIP_2</

SUBMITTER: Cao J 

PROVIDER: S-EPMC5595858 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature