The inhibitory effect of apolipoprotein E4 on neurite outgrowth is associated with microtubule depolymerization
Open accessAbstract
Evidence is presented for the differential effects of two isoforms of apolipoprotein (apo) E, apoE3 and apoE4, on neurite outgrowth and on the cytoskeleton of neuronal cells (Neuro-2a) in culture. In the presence of a lipid source, apoE3 enhances and apoE4 inhibits neurite outgrowth. Immunocytochemical studies demonstrate that there is a higher concentration of apoE3 than apoE4 in both the cell bodies and neurites. Cells treated with apoE4 showed fewer microtubules and a greatly reduced ratio of polymerized to monomeric tubulin than did cells treated with apoE3. The effect of apoE4 on depolymerization of microtubules was shown by biochemical, immunocytochemical, and ultrastructural studies. The depolymerization of microtubules and the inhibition of neurite outgrowth associated with apoE4 suggest a mechanism whereby apoE4, which has been linked to the pathogenesis of Alzheimer's disease, may prevent normal neuronal remodeling from occurring later in life, when this neurodegenerative disorder develops.
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The isoform-specific effect of apoE on neurite outgrowth could be secondary to its effect on microtubule organization, since the inhibitory effect of apoE4 on neurite outgrowth was closely associated with its detrimental effect on microtubule stability.
“The isoform-specific effect of apoE on neurite outgrowth could be secondary to its effect on microtubule organization, since the inhibitory effect of apoE4 on neurite outgrowth was closely associated with its detrimental effect on microtubule stability (Nathan et al., 1995).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Nathan et al., 1995
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- Authors
- Nathan, B. P., Chang, K.-C., Bellosta, S., Brisch, E., Ge, N., Mahley, R. W., & Pitas, R. E.
- Affiliations
- University of California, San Francisco (US)
- University of Kansas (US)
- Corresponding author
- Pitas, Robert E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-08
- Volume
- 270
- Issue
- 34
- Pages
- 19791-19799
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2158965128
- Cited by
- 276
- References
- 2
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 7 · 2012: 9
- FWCI
- 11.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- The Keep (Eastern Illinois University) (submittedVersion)
- Funders
- National Institutes of Health
- 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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- APOE ε4, apolipoprotein E3, neurite outgrowth, microtubule depolymerization, neuronal cytoskeleton, microtubule assembly, N2a cells, Alzheimer's disease, neuronal remodeling, lipid sources
- MeSH terms
- Actins, Alzheimer Disease, Animals, Apolipoproteins E, Cell Line, Immunohistochemistry, Microscopy, Electron, Microtubules, Polymers, Tubulin, Neurites, Mice, Apolipoprotein E3, Apolipoprotein E4
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