Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation
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 ɛ 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 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.
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Animal and cell models of tauopathies have revealed that APOE4 is associated with a greater burden of misfolded and hyperphosphorylated tau and more severe tau-induced neurodegeneration, both in the presence and in the absence of Aβ.
“Although for many years the effects of APOE on tau were assumed to be mediated through Aβ, animal and cell models of tauopathies have revealed that APOE4 is associated with a greater burden of misfolded and hyperphosphorylated tau and more severe tau-induced neurodegeneration, both in the presence and in the absence of Aβ125,126.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [125]
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ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
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Gardenia jasminoides J.Ellis extract GJ-4 alleviated cognitive deficits of APP/PS1 transgenic mice
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- Authors
- Hou, T.-T., Han, Y.-D., Cong, L., Liu, C.-C., Liang, X.-Y., Xue, F.-Z., & Du, Y.-F.
- Affiliations
- Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Internal Medicine, Shandong Police Hospital, Jinan, Shandong, China
- Shandong University (CN)
- Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, Shandong, China
- ORCID
- Cong, Lin
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2020-02-10
- Volume
- 74
- Issue
- 2
- Pages
- 521-534
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W3005704096
- Cited by
- 20
- References
- 6
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 1
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, APOE ε4
- MeSH terms
- Animals, Apolipoproteins E, Cells, Cultured, Cerebral Cortex, Male, Mice, Inbred C57BL, Mice, Transgenic, Phosphorylation, Amyloid beta-Peptides, tau Proteins, Mice, Knockout, Mice
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