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Cited by 370Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Apolipoprotein E, Receptors, and Modulation of Alzheimer’s Disease

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Zhao, Na, Liu, Chia-Chen, Qiao, Wenhui, Bu, Guojun·2018·Biological Psychiatry
DOI 10.1016/j.biopsych.2017.03.003PMC PMC5599322
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Abstract

Apolipoprotein E (apoE) is a lipid carrier in both the peripheral and the central nervous systems. Lipid-loaded apoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and injury repair in the brain. Considering prevalence and relative risk magnitude, the ε4 allele of the APOE gene is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE4 contributes to AD pathogenesis by modulating multiple pathways, including but not limited to the metabolism, aggregation, and toxicity of amyloid-β peptide, tauopathy, synaptic plasticity, lipid transport, glucose metabolism, mitochondrial function, vascular integrity, and neuroinflammation. Emerging knowledge on apoE-related pathways in the pathophysiology of AD presents new opportunities for AD therapy. We describe the biochemical and biological features of apoE and apoE receptors in the central nervous system. We also discuss the evidence and mechanisms addressing differential effects of apoE isoforms and the role of apoE receptors in AD pathogenesis, with a particular emphasis on the clinical and preclinical studies related to amyloid-β pathology. Finally, we summarize the current strategies of AD therapy targeting apoE, and postulate that effective strategies require an apoE isoform-specific approach.

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  • APOE4 is the strongest genetic determinant of late-onset AD, increasing risk in a gene dose-dependent manner, whereas APOE2 confers substantial protection.

    “APOE4 is the strongest genetic determinant of late-onset AD, increasing risk in a gene dose-dependent manner, whereas APOE2 confers substantial protection 1 -5 .”

    From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [4]

    The Abstract identifies APOE ε4 as the strongest genetic risk factor for late-onset Alzheimer’s disease and says ε2 is protective relative to ε3. The passages on Aβ deposition also describe a neuroprotective association for ε2. Our copy does not establish that AD risk rises with each ε4 allele or quantify the protection as substantial. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • APOE is predominantly expressed in glial cells, particularly astrocytes and activated microglia, which play central roles in Aβ accumulation, clearance, and neuroinflammation.

    “It is known that APOE is predominantly expressed in glial cells, particularly astrocytes and activated microglia, which play central roles in A β accumulation, clearance, and neuroin fl ammation 3,4 .”

    From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [4]

    The 'Biochemical features of apoE' section says that, in the CNS, apoE is highly expressed in astrocytes and microglia, but it does not specify activated microglia. The Aβ metabolism and clearance sections describe roles for apoE and glial cells in Aβ production and clearance. The copy does not establish the sentence’s broader assertion that these cells play central roles in neuroinflammation. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Astrocytes are the major cell type that express APOE in the brain.

    “it is the major cell type that express APOE in the brain (Zhao et al. 2018).”

    From Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport (2023) · cites this paper as Zhao et al. 2018

    The “Biochemical features of apoE” section says apoE is highly expressed in astrocytes in the CNS. It also lists other expressing cell types and does not establish that astrocytes are the major one; no page number is available in our copy. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Apolipoprotein E is the major lipoprotein in the brain for transporting lipids between cells.

    “Apolipoprotein E is the major lipoprotein in the brain for transporting lipids between cells (Zhao et al. 2018)”

    From Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport (2023) · cites this paper as Zhao et al. 2018

    The Biochemical features of apoE section (page not available) says apoE transports and delivers cholesterol and other lipids in the CNS through cell-surface receptors, and describes apoE-containing lipoprotein particles in the CNS. It does not establish that apoE is the major brain lipoprotein relative to others. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • APOE is the predominant intercellular transport system maintaining homeostasis of these lipids, especially when demand is unmet.

    “APOE is the predominant intercellular transport system to maintain the homeostasis of these lipids especially when such demand is unmet (Zhao et al. 2018).”

    From Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport (2023) · cites this paper as Zhao et al. 2018

    The “Biochemical features of apoE” section says apoE transports cholesterol and other lipids in plasma and the CNS through cell-surface receptors. It does not say apoE is the predominant intercellular transport system or that this role is especially important when lipid demand is unmet. No page number is available in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cites

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Authors
Zhao, N., Liu, C.-C., Qiao, W., & Bu, G.
Affiliations
  • Mayo Clinic in Florida (US)
  • Mayo Clinic (US)
Corresponding author
Bu, Guojun
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2018-02
Volume
83
Issue
4
Pages
347-357
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2017.03.003
PMC
PMC5599322
OpenAlex
W2601738889
Cited by
370
References
43
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FWCI
4.16
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journal article
Language
en
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www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • Israel Science Foundation
  • National Institute on Aging (RF1AG051504, R01AG027924, RF1AG046205, R01AG046205, R01AG035355, P50AG016574)
  • National Institute of Neurological Disorders and Stroke (P01NS074969)
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, Alzheimer's disease, apoE receptors, amyloid-beta, APOE isoforms, tauopathy, synaptic plasticity, lipid transport, glucose metabolism, mitochondrial function, neuroinflammation, vascular integrity
MeSH terms
Alzheimer Disease, Animals, Apolipoproteins E, Humans, Amyloid beta-Peptides, Low Density Lipoprotein Receptor-Related Protein-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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