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Cited by 94Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The role of APOE4 in Alzheimer’s disease: strategies for future therapeutic interventions

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Hunsberger, Holly C., Pinky, Priyanka D., Smith, Warren, Suppiramaniam, Vishnu, Reed, Miranda N.·2019·Neuronal Signaling
DOI 10.1042/ns20180203PMC PMC7104324
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Abstract

Alzheimer’s disease (AD) is the leading cause of dementia affecting almost 50 million people worldwide. The ε4 allele of Apolipoprotein E (APOE) is the strongest known genetic risk factor for late-onset AD cases, with homozygous APOE4 carriers being approximately 15-times more likely to develop the disease. With 25% of the population being APOE4 carriers, understanding the role of this allele in AD pathogenesis and pathophysiology is crucial. Though the exact mechanism by which ε4 allele increases the risk for AD is unknown, the processes mediated by APOE, including cholesterol transport, synapse formation, modulation of neurite outgrowth, synaptic plasticity, destabilization of microtubules, and β-amyloid clearance, suggest potential therapeutic targets. This review will summarize the impact of APOE on neurons and neuronal signaling, the interactions between APOE and AD pathology, and the association with memory decline. We will then describe current treatments targeting APOE4, complications associated with the current therapies, and suggestions for future areas of research and treatment.

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  • Proteinaceous lipid nanoparticles (LNPs) are the main vehicles for lipid transport between cells in mammals.

    “Proteinaceous lipid nanoparticles (LNPs) are the main vehicles for lipid transport between cells in mammals.1–4”

    From ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer’s Disease Pathogenesis (2025) · cites this paper as [2]

    The Introduction (page unavailable) says APOE circulates as part of a lipoprotein and plays an essential role in cholesterol and lipid metabolism. The section on APOE and mitochondrial function calls APOE a major modulator of cellular lipoprotein and cholesterol transport. Neither passage establishes that proteinaceous lipid nanoparticles are the main vehicles for lipid transport between cells throughout mammals. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Hunsberger, H. C., Pinky, P. D., Smith, W., Suppiramaniam, V., & Reed, M. N.
Affiliations
  • Research Foundation For Mental Hygiene (US)
  • Auburn University (US)
Corresponding author
Reed, Miranda N.
ORCID
Venue
Neuronal Signaling
Publisher
Portland Press Ltd.
Published
2019-04-18
Volume
3
Issue
2
Pages
NS20180203-NS20180203
ISSN
2059-6553 (ISSN-L)
DOI
10.1042/ns20180203
PMC
PMC7104324
OpenAlex
W2938259030
Cited by
94
References
23
Citations by year
2026: 20 · 2025: 18 · 2024: 23 · 2023: 15 · 2022: 10 · 2021: 3 · 2020: 4 · 2019: 1
FWCI
0.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuronal Signaling (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • 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
Alzheimer's disease, APOE ε4, apolipoprotein E, genetic risk factors, late-onset Alzheimer's disease, cholesterol transport, synaptogenesis, neurite outgrowth, synaptic plasticity, microtubule destabilization, amyloid-beta clearance, memory decline, therapeutic target, Alzheimer's disease treatment

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