Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation

Article type: Research Article

Authors: Hou, Ting-ting^a | Han, Yun-Dan^b | Cong, Lin^a | Liu, Cui-cui^a | Liang, Xiao-Yan^a | Xue, Fu-zhong^{c; *} | Du, Yi-feng^{a; *}

Affiliations: [a] Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China | [b] Department of Internal Medicine, Shandong Police Hospital, Jinan, Shandong, China | [c] Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, Shandong, China

Correspondence: [*] Correspondence to: Fu-zhong Xue, Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan 250012, P.R. China. Tel.: +86 13906405997; E-mail: xfzsdu@163.com. and Yi-feng Du, Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan 250021, P.R. China. Tel.: +86 13583118172; E-mail: du-yifeng@hotmail.com.

Abstract: 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-β (Aβ) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOE ɛ4, 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 Aβ oligomer (AβO) 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 ɛ4-treated apoE-/- neurons exhibited more phosphorylated tau than ApoE ɛ2- and ApoE ɛ3-treated neurons. We also found that AβO induced more serious inflammation in WT mice and in ApoE-positive cultured neurons. Anti-inflammatory treatment reduced the phosphorylated tau level induced by AβOs in ApoE-positive neurons. These results suggest that ApoE may facilitate the phosphorylation of tau induced by AβO via inflammation.

Keywords: Alzheimer’s disease, amyloid-β oligomer, apolipoprotein E, inflammation, phosphorylated tau

DOI: 10.3233/JAD-190711

Journal: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 521-534, 2020