Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation
Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation
复制标题
载脂蛋白 E 促进淀粉样蛋白 β 寡聚物诱导的 Tau 磷酸化
DOI：
10.3233/jad-190711
复制
发表时间：
2020-01-01
影响因子：
4
通讯作者：
Du, Yi-feng
中科院分区：
文献类型：
--
作者：
Hou, Ting-ting;Han, Yun-Dan;Du, Yi-feng
Hyperphosphorylated tau is one of the key characteristics of Alzheimer's disease (AD), and tau pathology correlates with cognitive impairment inADbetter than amyloid-beta (A beta) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOE epsilon 4, 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 A beta oligomer (A beta O) 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 epsilon 4-treated apoE(-/-) neurons exhibited more phosphorylated tau than ApoE epsilon 2- and ApoE epsilon 3-treated neurons. We also found that A beta O induced more serious inflammation in WT mice and in ApoE-positive cultured neurons. Anti-inflammatory treatment reduced the phosphorylated tau level induced by A beta Os in ApoE-positive neurons. These results suggest that ApoE may facilitate the phosphorylation of tau induced by A beta O via inflammation.
