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Cited by 41Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Neuronal ApoE4 in Alzheimer’s disease and potential therapeutic targets

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Zhang, Lan, Xia, Yiyuan, Gui, Yuran·2023·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2023.1199434PMC PMC10272394
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Abstract

The most prevalent genetic risk factor for Alzheimer’s disease (AD) is Apolipoprotein E (ApoE), a gene located on chromosome 19 that encodes three alleles (e2, e3, and e4) that give rise to the ApoE subtypes E2, E3, and E4, respectively. E2 and E4 have been linked to increased plasma triglyceride concentrations and are known to play a critical role in lipoprotein metabolism. The prominent pathological features of AD mainly include senile plaques formed by amyloid β (Aβ 42) aggregation and neuronal fibrous tangles (NFTs), and the deposited plaques are mainly composed of Aβ hyperphosphorylation and truncated head. In the central nervous system, the ApoE protein is primarily derived from astrocytes, but ApoE is also produced when neurons are stressed or affected by certain stress, injury, and aging conditions. ApoE4 in neurons induces Aβ and tau protein pathologies, leading to neuroinflammation and neuronal damage, impairing learning and memory functions. However, how neuronal ApoE4 mediates AD pathology remains unclear. Recent studies have shown that neuronal ApoE4 may lead to greater neurotoxicity, which increases the risk of AD development. This review focuses on the pathophysiology of neuronal ApoE4 and explains how neuronal ApoE4 mediates Aβ deposition, pathological mechanisms of tau protein hyperphosphorylation, and potential therapeutic targets.

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  • If and how neuronal APOE mediates AD pathophysiology remains unclear.

    “However, if and how neuronal APOE mediated AD pathophysiology remains unclear [7].”

    From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [7]

    The Abstract says that how neuronal ApoE4 mediates AD pathology remains unclear. But it also says neuronal ApoE4 induces Aβ and tau pathologies, so it does not present whether it contributes at all as unclear. The claim also broadens ApoE4 to neuronal APOE generally. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Zhang, L., Xia, Y., & Gui, Y.
Affiliations
Jianghan University (CN)
Corresponding author
Gui, Yuran
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2023-06-02
Volume
15
Pages
1199434-1199434
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2023.1199434
PMC
PMC10272394
OpenAlex
W4379233362
Cited by
41
References
38
Citations by year
2026: 7 · 2025: 17 · 2024: 12 · 2023: 5
FWCI
1.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Natural Science Foundation of Hubei Province (2022CFA104)
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
Alzheimer's disease, apolipoprotein E, APOE ε4, amyloid-beta, tau hyperphosphorylation, neuroinflammation, neurotoxicity, therapeutic target, lipoprotein metabolism, amyloid plaques, neurofibrillary tangles

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