Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein.
Open accessAbstract
Presence of the epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease (AD), although the mechanism(s) by which it confers this risk is unknown. ApoE may play a direct role in AD neuropathology by modulating neuronal structure. We previously showed that apoE3-containing beta-very low density lipoprotein (beta-VLDL) can stimulate neurite outgrowth to a significantly greater extent than apoE4-enriched beta-VLDL in a central nervous system-derived neuronal cell line and that this effect is mediated by interaction with the low density lipoprotein receptor-related protein (LRP). To determine whether similar differences exist when apoE is associated with other lipoprotein particles, the effects of high density lipoprotein (HDL) derived from plasma and cerebrospinal fluid were defined. ApoE3-enriched HDL significantly enhanced neurite outgrowth as compared with apoE4-enriched HDL, and the majority of this stimulation was blocked in the presence of the receptor-associated protein or a neutralizing antibody to LRP. We also found that cholesterol esterification in the presence of apoE-containing plasma HDL was attenuated in fibroblasts lacking LRP. Therefore, apoE-containing HDL can serve as an LRP ligand, and apoE isoform-specific effects on neurite outgrowth are observed when HDL is the carrier particle.
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The stimulation of neurite outgrowth by apoE is, in part, mediated by LRP1.
“The stimulation of neurite outgrowth by apoE is, in part, mediated by LRP1 (Fagan et al., 1996; Holtzman et al., 1995; Narita et al., 1997; Nathan et al., 2002).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Fagan et al., 1996
The stimulation of neurite outgrowth by apoE may be mediated by LRP1 or other apoE receptors.
“The stimulation of neurite outgrowth by apoE may be mediated by LRP1 (Fagan et al., 1996; Holtzman et al., 1995; Narita et al., 1997; Nathan et al., 2002) or other apoE receptors (DeMattos et al., 1998; Puttfarcken et al., 1997).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Fagan et al., 1996
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References 36 · Cited by 226
Research works printed but not linked: 9
- Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Eng- hild, J., Salvesen, G. S., and Roses, A. D. (1993) Proc. Natl. Acad. Sci.
- Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper- MacLachlan, D. R., Alberts, M. J., Hulette, C., Crain, B., Goldgaber, D., and Roses, A. D. (1993) Neurology 43, 1467-1472
- Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., and Pericak-Vance, M. A. (1993) Science 261, 921-923
- Elshourbagy, N. A., Liao, W. S., Mahley, R. W., and Taylor, J. M. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 203-207
- Ignatius, M. J., Gebicke-Harter, P. J., Skene, J. H. P., Schilling, J. W., Weis- graber, K. H., Mahley, R. W., and Shooter, E. M. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 1125-1129
- Snipes, G. J., McGuire, C. B., Norden, J. J., and Freeman, J. A. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 1130 -1134
- Holtzman, D. M., Pitas, R. E., Kilbridge, J., Nathan, B., Mahley, R. W., Bu, G., and Schwartz, A. L. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 9480 -9484
- Roheim, P. S., Carey, M., Forte, T., and Vega, G. L. (1979) Proc. Natl. Acad. Sci. U. S. A. 76, 4646 -4649
- Zhou, J., Holtzman, D. M., Weiner, R., and Mobley, W. C. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 3824 -3828
- Authors
- Fagan, A. M., Bu, G., Sun, Y., Daugherty, A., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Fagan, Anne M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-11
- Volume
- 271
- Issue
- 47
- Pages
- 30121-30125
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2012436641
- Cited by
- 226
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 6
- FWCI
- 11.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Alzheimer's Association
- American Federation for Aging Research
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, high-density lipoprotein, neurite outgrowth, low density lipoprotein receptor-related protein, APOE ε4, APOE3, Alzheimer's disease, cholesterol esterification, lipoprotein receptors, neuronal cell lines
- MeSH terms
- Apolipoproteins E, Cell Line, Cholesterol Esters, Humans, Ligands, Lipoproteins, HDL, Protein Binding, Receptors, Immunologic, Neurites, Low Density Lipoprotein Receptor-Related Protein-1
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