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Cited by 23Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Nuclear Localization of Apolipoprotein E4: A New Trick for an Old Protein

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Rohn, Troy T·2017·International Journal of Neurology and Neurotherapy
DOI 10.23937/2378-3001/1410067PMC PMC5734658
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Abstract

One of the most important genetic risk factors for late-onset Alzheimer’s Disease (AD) is harboring the APOE4 allele. Much is known regarding the functions of the apoE4 protein including cholesterol transport in the CNS and a critical role in clearing beta-amyloid deposits in the AD brain. However, recent studies demonstrating the nuclear localization suggest a novel function beyond the classical known actions of apoE4.

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Crossref · 10.23937/2378-3001/1410067

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  • Microglial APOE4 shows increased nuclear localization in AD brains.

    “Furthermore, microglial APOE4 shows increased nuclear localization in AD brains 45 .”

    From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [45]

    The “Nuclear Localization of ApoE4” section reports strong labeling of an ApoE4 fragment within microglia in AD brain tissue and nuclear trafficking of that fragment in cultured microglial cells. The “Mechanism of Nuclear Trafficking of ApoE” section also reports nuclear labeling in AD brain tissue. Neither passage establishes that nuclear localization is increased in microglia of AD brains relative to a comparator. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • ApoE4 N-terminal fragments (1-151 aa) translocate to the nucleus and act as a transcription factor, promoting Alzheimer's disease pathogenesis.

    “Other authors demonstrated that N-terminal fragments of ApoE4 (1–151 aa) translocate to the nucleus and act as a transcription factor (Figure 1), promoting AD pathogenesis [25]”

    From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [25]

    The Nuclear Localization of ApoE4 section reports that an ApoE4 1–151 fragment entered the nuclei of BV2 cells and caused toxicity. But it calls the resulting gene-expression pathway putative; the Concluding Remarks say fragments *may* serve as transcription factors and that this role needs confirmation. The claim therefore overstates both the fragment’s demonstrated transcription-factor activity and its proposed contribution to AD pathogenesis. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • This transcriptional deregulation triggers processes such as synaptic dysfunction, inflammation and neuronal death, which contribute to development of AD.

    “This transcriptional deregulation triggers processes such as synaptic dysfunction, inflammation and neuronal death [25], which contribute to the development of AD.”

    From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [25]

    The Concluding Remarks (page not available) propose that nuclear ApoE4 may activate genes involved in programmed cell death and inflammation, potentially linking this mechanism to AD risk. The paper discusses effects on synaptic plasticity separately, in relation to cholesterol transport, not as a consequence of transcriptional deregulation. It also presents the transcriptional pathway as a possibility rather than an established trigger. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • APOE4 acquires a novel function in the nucleus, where it translocates and directly binds DNA to affect transcription of genes associated with AD.

    “In addition to the classical role of APOE in cholesterol transport, APOE4 acquires a novel function in the nucleus, where it translocates and directly binds DNA to affect the transcription of genes associated with AD 45,46 .”

    From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [45]

  • Carrying the ε4 allele of APOE is linked to an earlier and more extensive formation of senile plaques.

    “carrying the ε4 allele of APOE gene is linked to an earlier and more extensive formation of senile plaques [25]”

    From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [25]

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Cites

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Research works printed but not linked: 33

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Authors
Rohn, T. T.
Affiliations
Boise State University (US)
Corresponding author
Rohn, Troy T
ORCID
Rohn, Troy T
Venue
International Journal of Neurology and Neurotherapy
Publisher
ClinMed International Library
Published
2017-12-31
Volume
4
Issue
2
ISSN
2378-3001 (ISSN-L)
DOI
10.23937/2378-3001/1410067
PMC
PMC5734658
OpenAlex
W2762450062
Cited by
23
References
8
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 3
FWCI
1.21
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • International Journal of Neurology and Neurotherapy (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
  • National Institutes of Health
  • National Institute on Aging (R15AG042781)
  • National Institute of General Medical Sciences (P20GM109095, P20GM103408)
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
APOE ε4, nuclear localization, Alzheimer's disease, genetic risk factors, amyloid-beta clearance, cholesterol transport

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