Differential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Abstract
Apolipoprotein E4 (apoE4), one of the three common isoforms of apoE, has been implicated in Alzheimer's disease. The effects of apoE on neuronal growth were determined in cultures of dorsal root ganglion neurons. In the presence of beta-migrating very low density lipoproteins (beta-VLDL), apoE3 increased neurite outgrowth, whereas apoE4 decreased outgrowth. The effects of apoE3 or apoE4 in the presence of beta-VLDL were prevented by incubation with a monoclonal antibody to apoE or by reductive methylation of apoE, both of which block the ability of apoE to interact with lipoprotein receptors. The data suggest that receptor-mediated binding or internalization (or both) of apoE-enriched beta-VLDL leads to isoform-specific differences in interactions with cellular proteins that affect neurite outgrowth.
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APOE4 has been observed to exhibit enhanced receptor binding and/or signaling.
“In contrast, APOE4 has been observed to exhibit enhanced receptor binding and/or signaling9,34.”
From Common germline variants of the human APOE gene modulate melanoma progression and survival (2020) · cites this paper as [34]
Most studies have shown that apoE3 augments neurite outgrowth to a greater extent than apoE4.
“Most studies have shown that apoE3 augments neurite outgrowth to a greater extent than apoE4 (Bellosta et al., 1995; Nathan et al., 1994; Nathan et al., 2002; Sun et al., 1998; Teter et al., 1999).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Nathan et al., 1994
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- Authors
- Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Science
- Published
- 1994-05-06
- Volume
- 264
- Issue
- 5160
- Pages
- 850-852
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1997913988
- Cited by
- 795
- References
- 4
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 9 · 2020: 12 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 18 · 2015: 11 · 2014: 17 · 2013: 14 · 2012: 10
- FWCI
- 31.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- The Keep (Eastern Illinois University) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-41633, P01HL041633)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- apolipoprotein E, apolipoprotein E3, APOE ε4, neurite outgrowth, dorsal root ganglion neurons, beta-VLDL, lipoprotein receptors, Alzheimer's disease, receptor internalization, monoclonal antibodies, reductive methylation, neuronal growth
- MeSH terms
- Animals, Apolipoproteins E, Cells, Cultured, Fetus, Ganglia, Spinal, Lipoproteins, VLDL, Neurons, Rabbits, Receptors, LDL, Neurites, Culture Media, Serum-Free, Apolipoprotein E3, Apolipoprotein E4
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