Apolipoprotein E and apolipoprotein E receptors modulate Aβ-induced glial neuroinflammatory responses
Abstract
Large numbers of activated glia are a common pathological feature of many neurodegenerative disorders, including Alzheimer's disease (AD). Several different stimuli, including lipopolysaccharide (LPS), dibutyryl (db)cAMP, and aged amyloid-beta 1-42 (A beta), can induce glial activation in vitro, as measured by morphological changes and the production of pro-inflammatory cytokines and oxidative stress molecules. Only A beta-induced activation is attenuated by the addition of exogenous apolipoprotein E (apoE)-containing particles. In addition, only A beta also induces an increase in the amount of endogenous apoE, the primary apolipoprotein expressed by astrocytes in the brain. The functional significance of the increase in apoE appears to be to limit the inflammatory response. Indeed, compared to wild type mice, glial cells cultured from apoE knockout mice exhibit an enhanced production of several pro-inflammatory markers in response to treatment with A beta and other activating stimuli. The mechanism for both the A beta-induced glial activation and the increase in apoE appears to involve apoE receptors, a variety of which are expressed by both neurons and glia. Experiments using receptor associated protein (RAP), an inhibitor of apoE receptors with a differential affinity for the low-density lipoprotein receptor (LDLR) and the LDLR-related protein (LRP), revealed that LRP mediates A beta-induced glial activation, while LDLR mediates the A beta-induced changes in apoE levels. I…
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Aβ induces the production of apoE.
“Interestingly, Aβ induces the production of apoE and the increased levels of apoE limit Aβ-driven neuroinflammation, possibly functioning as a feedback mechanism (Guo et al., 2004; LaDu et al., 2001).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as LaDu et al., 2001
Increased levels of apoE limit Aβ-driven neuroinflammation, possibly functioning as a feedback mechanism.
“and the increased levels of apoE limit Aβ-driven neuroinflammation, possibly functioning as a feedback mechanism (Guo et al., 2004; LaDu et al., 2001).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as LaDu et al., 2001
Cites
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · see citing works
Oda, T., Wals, P., Osterburg, H. H., Johnson, S. A., Pasinetti, G. M., Morgan, T. E., Rozovsky, I., Stine, W. B., Snyder, S. W., Holzman, T. F., et al. (1995) · Experimental Neurology · doi:10.1006/exnr.1995.1080 · Cited by 352 · see citing works
Nascent astrocyte particles differ from lipoproteins in CSF
LaDu, M. J., Gilligan, S. M., Lukens, J. R., Cabana, V. G., Reardon, C. A., Van Eldik, L. J., & Holtzman, D. M. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052070.x · Cited by 285 · cited 1× · see citing works
“We have previously reported (LaDu et al., 1998) that rat glial cells secrete HDL-like lipoprotein particles with apoE and apoJ as the primary protein components.”
Sun, Y., Wu, S., Bu, G., Onifade, M. K., Patel, S. N., LaDu, M. J., Fagan, A. M., & Holtzman, D. M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-09-03261.1998 · Cited by 213 · see citing works
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Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
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Emery, D. C., Shoemark, D. K., Batstone, T. E., Waterfall, C. M., Coghill, J. A., Cerajewska, T. L., Davies, M., West, N. X., & Allen, S. J. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00195 · Cited by 317 · see citing works
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Uddin, M. S., Kabir, M. T., Al Mamun, A., Abdel-Daim, M. M., Barreto, G. E., & Ashraf, G. M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1237-z · Cited by 212 · see citing works
Tai, L. M., Ghura, S., Koster, K. P., Liakaite, V., Maienschein‐Cline, M., Kanabar, P., Collins, N., Ben‐Aissa, M., Lei, A. Z., Bahroos, N., et al. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13072 · Cited by 165 · see citing works
Self-citationWilhelmus, M. M. M., Otte-Höller, I., van Triel, J. J. J., Veerhuis, R., Maat-Schieman, M. L. C., Bu, G., de Waal, R. M. W., & Verbeek, M. M. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070050 · Cited by 138 · see citing works
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Sleegers, K., Lambert, J.-C., Bertram, L., Cruts, M., Amouyel, P., & Van Broeckhoven, C. (2010) · Trends in Genetics · doi:10.1016/j.tig.2009.12.004 · Cited by 129 · see citing works
Apolipoprotein E and Alzheimer's disease: the protective effects of ApoE2 and E3
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Manelli, A. M., Bulfinch, L. C., Sullivan, P. M., & LaDu, M. J. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.024 · Cited by 72 · see citing works
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Rebeck, G. W., LaDu, M. J., Estus, S., Bu, G., & Weeber, E. J. (2006) · Molecular Neurodegeneration · doi:10.1186/1750-1326-1-15 · Cited by 66 · see citing works
Self-citationAstrocytes: a cellular player in Aβ clearance and degradation
Guénette, S. Y. (2003) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(03)00112-6 · Cited by 64 · see citing works
Apolipoprotein E decreases tau kinases and phospho-tau levels in primary neurons.
Hoe, H.-S., Freeman, J., & Rebeck, G. W. (2006) · Molecular Neurodegeneration · doi:10.1186/1750-1326-1-18 · Cited by 45 · see citing works
- Authors
- LaDu, M. J., Shah, J. A., Reardon, C. A., Getz, G. S., Bu, G., Hu, J., Guo, L., & Van Eldik, L. J.
- Affiliations
- Northwestern University (US)
- University of Chicago (US)
- Washington University in St. Louis (US)
- Corresponding author
- LaDu, Mary Jo
- Venue
- Neurochemistry International
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 39
- Issue
- 5-6
- Pages
- 427-434
- ISSN
- 0197-0186 (ISSN-L)
- OpenAlex
- W2151937352
- Cited by
- 118
- References
- 5
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 8 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 3
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemistry International (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Brain Research Foundation
- American Health Assistance Foundation
- National Institutes of Health (5r01ns037525-04)
- National Institute on Aging (AG16776)
- National Institute of Neurological Disorders and Stroke (NS 37525)
- 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 E receptor, amyloid-beta, glial activation, neuroinflammation, Alzheimer's disease, astrocytes, LDL receptor, receptor-associated protein, inflammatory cytokines, oxidative stress, ApoE-deficient mice
- MeSH terms
- Animals, Apolipoproteins E, Encephalitis, Humans, Neuroglia, Amyloid beta-Peptides, Low Density Lipoprotein Receptor-Related Protein-1
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