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Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation.
- Source :
- Journal of Alzheimer's Disease; 2020, Vol. 74 Issue 2, p521-534, 14p
- Publication Year :
- 2020
-
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. APOEɛ4, 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13872877
- Volume :
- 74
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Alzheimer's Disease
- Publication Type :
- Academic Journal
- Accession number :
- 142397317
- Full Text :
- https://doi.org/10.3233/JAD-190711