The ApoE receptors Vldlr and Apoer2 in central nervous system function and disease
Open accessAbstract
The LDL receptor (LDLR) family has long been studied for its role in cholesterol transport and metabolism; however, the identification of ApoE4, an LDLR ligand, as a genetic risk factor for late-onset Alzheimer's disease has focused attention on the role this receptor family plays in the CNS. Surprisingly, it was discovered that two LDLR family members, ApoE receptor 2 (Apoer2) and VLDL receptor (Vldlr), play key roles in brain development and adult synaptic plasticity, primarily by mediating Reelin signaling. This review focuses on Apoer2 and Vldlr signaling in the CNS and its role in human disease.
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ApoE isoforms differentially perturb endosomal recycling of receptors such as LRP8/ApoER2, with ApoE4 having a deleterious impact on reelin signaling.
“Previous work showed ApoE isoforms differentially perturb endosomal recycling of receptors, such as LRP8/ApoER2, with a deleterious impact of ApoE4 on signaling by reelin, a key ligand of this receptor49.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [49]
Cites
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 1× · see citing works
“Reelin activation of downstream kinases and enhancement of LTP is important for protection against A, which reduces LTP by enhancing NMDAR endocytosis via striatalenriched protein tyrosine phosphatase (80).”
Hiesberger, T., Trommsdorff, M., Howell, B. W., Goffinet, A., Mumby, M. C., Cooper, J. A., & Herz, J. (1999) · Neuron · doi:10.1016/s0896-6273(00)80861-2 · Cited by 916 · see citing works
Self-citationOgawa, M., Miyata, T., Nakajimat, K., Yagyu, K., Seike, M., Ikenaka, K., Yamamoto, H., & Mikoshibat, K. (1995) · Neuron · doi:10.1016/0896-6273(95)90329-1 · Cited by 889 · cited 1× · see citing works
“In the prenatal brain, Reelin is secreted by Cajal-Retzius cells in the marginal zone of the cortex, where it sends signals to migrating neurons, leading to the characteristic “inside-out” pattern of the cortex, whereby the youngest neurons are in the most superficial layers and the oldest neurons are in the deepest l…”
BackgroundFalconer, D. S. (1951) · Journal of Genetics · doi:10.1007/bf02996215 · Cited by 539 · see citing works
Beffert, U., Weeber, E. J., Durudas, A., Qiu, S., Masiulis, I., Sweatt, J. D., Li, W.-P., Adelmann, G., Frotscher, M., Hammer, R. E., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.07.007 · Cited by 497 · see citing works
Self-citationFiore, F., Zambrano, N., Minopoli, G., Donini, V., Duilio, A., & Russo, T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.52.30853 · Cited by 294 · see citing works
Proteins of the CNR Family Are Multiple Receptors for Reelin
Senzaki, K., Ogawa, M., & Yagi, T. (1999) · Cell · doi:10.1016/s0092-8674(00)81552-4 · Cited by 272 · see citing works
Dean, D. C., Jerskey, B. A., Chen, K., Protas, H., Thiyyagura, P., Roontiva, A., O'Muircheartaigh, J., Dirks, H., Waskiewicz, N., Lehman, K., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2013.4544 · Cited by 263 · see citing works
DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing
Hoe, H.-S., Tran, T. S., Matsuoka, Y., Howell, B. W., & Rebeck, G. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602162200 · Cited by 174 · see citing works
ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease
Lane-Donovan, C., & Herz, J. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.12.001 · Cited by 157 · see citing works
Self-citationReelin signaling antagonizes β-amyloid at the synapse
Durakoglugil, M. S., Chen, Y., White, C. L., Kavalali, E. T., & Herz, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908176106 · Cited by 153 · see citing works
Self-citationUtsunomiya-Tate, N., Kubo, K.-I., Tate, S.-I., Kainosho, M., Katayama, E., Nakajima, K., & Mikoshiba, K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.160272497 · Cited by 131 · cited 1× · see citing works
“However, the N-t fragment is required for homodimerization of Reelin (24, 25), while the C-terminal fragment is required for full Reelin signaling (26).”
BackgroundMak, A. C. Y., Pullinger, C. R., Tang, L. F., Wong, J. S., Deo, R. C., Schwarz, J.-M., Gugliucci, A., Movsesyan, I., Ishida, B. Y., Chu, C., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.2011 · Cited by 96 · see citing works
Reelin protects against amyloid β toxicity in vivo
Lane-Donovan, C., Philips, G. T., Wasser, C. R., Durakoglugil, M. S., Masiulis, I., Upadhaya, A., Pohlkamp, T., Coskun, C., Kotti, T., Steller, L., et al. (2015) · Science Signaling · doi:10.1126/scisignal.aaa6674 · Cited by 96 · see citing works
Self-citationFE65 interaction with the ApoE receptor ApoEr2
Hoe, H.-S., Magill, L. A., Guenette, S., Fu, Z., Vicini, S., & Rebeck, G. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600728200 · Cited by 69 · see citing works
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Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425 · see citing works
Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability
Li, Z., Ferguson, L., Deol, K. K., Roberts, M. A., Magtanong, L., Hendricks, J. M., Mousa, G. A., Kilinc, S., Schaefer, K., Wells, J. A., et al. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01033-3 · Cited by 134 · see citing works
Guo, J. L., Braun, D., Fitzgerald, G. A., Hsieh, Y.-T., Rougé, L., Litvinchuk, A., Steffek, M., Propson, N. E., Heffner, C. M., Discenza, C., et al. (2025) · Cell · doi:10.1016/j.cell.2024.10.027 · Cited by 91 · see citing works
“49 Our study now demonstrates lipApoE isoform-dependent impact on the endolysosomal traf-ficking of a distinct ApoE receptor, LDLR, which primarily mediates lipid metabolism.”
ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease
Li, Y., Macyczko, J. R., Liu, C.-C., & Bu, G. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.03.011 · Cited by 61 · see citing works
- Authors
- Lane-Donovan, C., & Herz, J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Herz, Joachim
- ORCID
- Herz, Joachim
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 58
- Issue
- 6
- Pages
- 1036-1043
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC5454520
- OpenAlex
- W2604425979
- Cited by
- 94
- References
- 16
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 14 · 2023: 11 · 2022: 12 · 2021: 12 · 2020: 12 · 2019: 7 · 2018: 5 · 2017: 4
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (F30-AG047799, HL063762, NS093382, AG053391)
- the Consortium for Frontotemporal Dementia Research
- BrightFocus Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- VLDLR, APOE ε4, LDL receptor family, Reelin signaling, synaptic plasticity, brain development, Alzheimer's disease, cholesterol transport, central nervous system
- MeSH terms
- Reelin Protein, Animals, Central Nervous System, Central Nervous System Diseases, Humans, Receptors, LDL, Signal Transduction, Alternative Splicing, Low Density Lipoprotein Receptor-Related Protein-1
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