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Cited by 34Alzheimer's disease research and treatmentsOlfactory and Sensory Function StudiesNeurogenesis and neuroplasticity mechanisms

Isoform-specific effects of apoE on neurite outgrowth in olfactory epithelium culture

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Hussain, Aseem, Luong, Minh, Pooley, Apryl, Nathan, Britto P·2013·Journal of Biomedical Science
DOI 10.1186/1423-0127-20-49PMC PMC3717083
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Abstract

Background: The apolipoprotein E4 (apoE4) genotype is a major risk factor for developing late-onset Alzheimer’s disease (AD). Inheritance of apoE4 is also associated with impairments in olfactory function in early stages of AD. In this project we examined the effects of the three common isoforms of human apoE (apoE2, apoE3, and apoE4) on neuronal differentiation and neurite outgrowth in explant cultures of mouse olfactory epithelium (OE). Results: The OE cultures derived from apoE-deficient/knockout (KO) mice have significantly fewer neurons with shorter neurite outgrowth than cultures from wild-type (WT) mice. Treatment of the apoE KO culture with either purified human apoE2 or with human apoE3 significantly increased neurite outgrowth. In contrast, treatment with apoE4 did not have an effect on neurite outgrowth. The differential effects of human apoE isoforms on neurite outgrowth were abolished by blocking the low-density lipoprotein receptor-related protein (LRP) with lactoferrin and receptor-associated protein (RAP). Conclusion: ApoE2 and apoE3 stimulate neurite outgrowth in OE cultures by interacting with the lipoprotein receptor, LRP. ApoE4, the isoform associated with AD, failed to promote neurite outgrowth, suggesting a potential mechanism whereby apoE4 may lead to olfactory dysfunction in AD patients.

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  • APOE has been shown to directly regulate neurite outgrowth in an isoform-dependent manner, with APOE4 inhibiting neurite extension in multiple systems.

    “APOE has been shown to directly regulate neurite outgrowth in an isoform-dependent manner, with APOE4 inhibiting neurite extension in multiple systems (Hussain et al., 2013; Nathan et al., 2002; Zhao et al., 2017).”

    From APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells (2026) · cites this paper as Hussain et al., 2013

    The Results and discussion section reports isoform-dependent effects and notes that other studies found apoE4 decreased neurite outgrowth in cell lines and dissociated cultures. But in this paper’s olfactory-epithelium cultures, apoE4 had no effect relative to medium alone; the authors also leave open whether apoE acts directly or indirectly. Thus the claim overstates what this study itself showed. (LLM, conf=0.88)

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Cited by

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Authors
Hussain, A., Luong, M., Pooley, A., & Nathan, B. P.
Affiliations
Eastern Illinois University (US)
Corresponding author
Nathan, Britto P
ORCID
Venue
Journal of Biomedical Science
Publisher
Springer Science and Business Media LLC
Published
2013-07-12
Volume
20
Issue
1
Pages
49-49
ISSN
  • 1021-7770 (ISSN-L)
  • 1423-0127
DOI
10.1186/1423-0127-20-49
PMC
PMC3717083
OpenAlex
W2159474448
Cited by
34
References
4
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 3 · 2015: 6 · 2014: 2
FWCI
1.85
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Biomedical Science (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Journal of Collective Bargaining in the Academy (submittedVersion)
  • The Keep (Eastern Illinois University) (submittedVersion)
Funders
Eastern Illinois University
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
apolipoprotein E, APOE isoforms, APOE ε4, neurite outgrowth, olfactory epithelium, neuronal differentiation, Alzheimer's disease, olfactory dysfunction, low density lipoprotein receptor-related protein, lactoferrin, receptor-associated protein, ApoE-deficient mice
MeSH terms
Animals, Apolipoproteins E, Cell Line, Humans, Olfactory Mucosa, Neurites, Mice, Knockout, Protein Isoforms, Mice, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2

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