Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation

Hyperphosphorylated tau is one of the key characteristics of Alzheimer's disease (AD), and tau pathology correlates with cognitive impairment in AD better than amyloid-beta (Abeta) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOEvarepsilon4, the strongest genetic risk factor for AD, was found to be involved in tau pathology in frontotemporal dementia. This result indicated that apolipoprotein E (ApoE) may also participate in tau phosphorylation in AD. In the present study, we injected Abeta oligomer (AbetaO) into the lateral ventricles of wild-type (WT) mice and apoE-/- mice to test the process of tau phosphorylation in the acute phase. We found that the phosphorylated tau and phosphokinase levels were higher in WT mice than in apoE-/- mice. These phenomena were also confirmed in vitro. ApoE varepsilon4-treated apoE-/- neurons exhibited more phosphorylated tau than ApoE varepsilon2- and ApoE varepsilon3-treated neurons. We also found that AbetaO induced more serious inflammation in WT mice and in ApoE-positive cultured neurons. Anti-inflammatory treatment reduced the phosphorylated tau level induced by AbetaOs in ApoE-positive neurons. These results suggest that ApoE may facilitate the phosphorylation of tau induced by AbetaO via inflammation.