Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain.
Open accessAbstract
This study was undertaken to determine if apolipoprotein (apo) E-containing lipoproteins and their receptors could provide a system for lipid transport and cholesterol homeostasis in the brain, as they do in other tissues. To accomplish this goal, the lipoproteins in human and canine cerebrospinal fluid (CSF) were characterized, and rat brain and monkey brain were examined for the presence of apoB,E(LDL) receptors. Apolipoprotein E and apoA-I were present in human and canine CSF, but apoB could not be detected. Apo-lipoprotein E and apoA-I were both present on lipoproteins with a density of approximately 1.09 to 1.15 g/ml. In human CSF, the lipoproteins were primarily spherical (approximately 140 A), whereas in canine CSF the lipoproteins were a mixture of discs (200 x 65 A) and spheres (approximately 130 A). Apolipoproteins E and A-I were contained primarily in separate populations of lipoproteins. Although the apoE of CSF was more highly sialylated than plasma apoE, the apoE-containing lipoproteins in canine CSF competed as effectively as canine plasma apoE HDLc for binding of 125I-LDL to the apoB,E(LDL) receptors on human fibroblasts. The presence of apoB,E(LDL) receptors in both rat and monkey brain was demonstrated by immunocytochemistry. Astrocytes abutting on the arachnoid space and pial cells of the arachnoid itself, both of which contact CSF, expressed apoB,E(LDL) receptors. Relatively few receptors were present in the cells of the gray matter of the cortex. Receptor…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ApoE plays a central role in brain lipid homeostasis by mediating endocytosis of HDL-like lipoprotein particles.
“ApoE plays a central role in brain lipid homeostasis by mediating the endocytosis of HDL-like lipoprotein particles (30).”
From The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis (2015) · cites this paper as [30]
Non-neuronal cells, mainly astrocytes and to some extent microglia, are the major cell types that express apoE in the brain.
“Non-neuronal cells, mainly astrocytes and to some extent microglia, are the major cell types that express apoE in the brain (Grehan et al., 2001; Pitas et al., 1987).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Pitas et al., 1987
The predominant apolipoprotein of HDL in the central nervous system is apoE.
“Unlike plasma HDL that contains apoA-1 as its major apolipoprotein, the predominant apolipoprotein of HDL in the central nervous system (CNS) is apoE (Pitas et al., 1987).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Pitas et al., 1987
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703 · see citing works
Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins
Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D., & Mahley, R. W. (1987) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(87)90295-5 · Cited by 693 · see citing works
Self-citationProposed nomenclature of apoE isoproteins, apoE genotypes, and phenotypes
Zannis, V. I., Breslow, J. L., Utermann, G., Mahley, R. W., Weisgraber, K. H., Havel, R. J., Goldstein, J. L., Brown, M. S., Schonfeld, G., Hazzard, W. R., et al. (1982) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38094-9 · Cited by 436 · see citing works
Self-citationThe receptor-binding domain of human apolipoprotein E. Binding of apolipoprotein E fragments.
Innerarity, T. L., Friedlander, E. J., Rall, S. C., Weisgraber, K. H., & Mahley, R. W. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44180-9 · Cited by 276 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · see citing works
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028 · see citing works
The role of apolipoprotein E in Alzheimer's disease
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
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168 · see citing works
Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E., & Ikeda, K. (1991) · Brain Research · doi:10.1016/0006-8993(91)91092-f · Cited by 1,157 · see citing works
Brain Cholesterol: Long Secret Life Behind a Barrier
Björkhem, I., & Meaney, S. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000120374.59826.1b · Cited by 1,044 · see citing works
Essential fatty acids in growth and development
Innis, S. M. (1991) · Progress in Lipid Research · doi:10.1016/0163-7827(91)90006-q · Cited by 921 · see citing works
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912 · see citing works
Self-citationApolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857 · see citing works
Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity
Ioannou, M. S., Jackson, J., Sheu, S.-H., Chang, C.-L., Weigel, A. V., Liu, H., Pasolli, H. A., Xu, C. S., Pang, S., Matthies, D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.04.001 · Cited by 760 · see citing works
ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608 · see citing works
Isoform-specific binding of apolipoprotein E to beta-amyloid.
LaDu, M. J., Falduto, M. T., Manelli, A. M., Reardon, C. A., Getz, G. S., & Frail, D. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31529-6 · Cited by 540 · see citing works
Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism
Mahley, R. W. (2016) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.116.307023 · Cited by 516 · see citing works
Reelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524 · see citing works
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524 · see citing works
Cholesterol metabolism in neurons and astrocytes
Pfrieger, F. W., & Ungerer, N. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2011.06.002 · Cited by 500 · see citing works
Genetic Association of Apolipoprotein E with Age-Related Macular Degeneration
Klaver, C. C. W., Kliffen, M., van Duijn, C. M., Hofman, A., Cruts, M., Grobbee, D. E., van Broeckhoven, C., & de Jong, P. T. V. M. (1998) · The American Journal of Human Genetics · doi:10.1086/301901 · Cited by 498 · see citing works
Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.
Linton, M. F., Gish, R., Hubl, S. T., Bütler, E., Esquivel, C., Bry, W. I., Boyles, J. K., Wardell, M. R., & Young, S. G. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115288 · Cited by 367 · see citing works
Self-citationAmyloid β-Peptide Is Transported on Lipoproteins and Albumin in Human Plasma
Biere, A. L., Ostaszewski, B., Stimson, E. R., Hyman, B. T., Maggio, J. E., & Selkoe, D. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32916 · Cited by 331 · see citing works
Human Apolipoprotein E4 Domain Interaction
Dong, L.-M., & Weisgraber, K. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19053 · Cited by 318 · see citing works
Self-citationCholesterol in brain disease: Sometimes determinant and frequently implicated
Martín, M. G., Pfrieger, F., & Dotti, C. G. (2014) · The EMBO Reports · doi:10.15252/embr.201439225 · Cited by 304 · see citing works
Characterization of four lipoprotein classes in human cerebrospinal fluid
Koch, S., Donarski, N., Goetze, K., Kreckel, M., Stuerenburg, H.-J., Buhmann, C., & Beisiegel, U. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31605-9 · Cited by 298 · see citing works
Huang, Y., Weisgraber, K. H., Mucke, L., & Mahley, R. W. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:3:189 · Cited by 242 · see citing works
Self-citationFagan, A. M., Holtzman, D. M., Munson, G., Mathur, T., Schneider, D., Chang, L. K., Getz, G. S., Reardon, C. A., Lukens, J., Shah, J. A., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.30001 · Cited by 222 · see citing works
Gong, J.-S., Kobayashi, M., Hayashi, H., Zou, K., Sawamura, N., Fujita, S. C., Yanagisawa, K., & Michikawa, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203934200 · Cited by 214 · see citing works
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
Targeting microglia for the treatment of Alzheimer’s Disease
Wes, P. D., Sayed, F. A., Bard, F., & Gan, L. (2016) · Glia · doi:10.1002/glia.22988 · Cited by 185 · see citing works
Sources of eicosanoid precursor fatty acid pools in tissues
Zhou, L., & Nilsson, Å. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32206-9 · Cited by 184 · see citing works
DeMattos, R. B., Brendza, R. P., Heuser, J. E., Kierson, M., Cirrito, J. R., Fryer, J., Sullivan, P. M., Fagan, A. M., Han, X., & Holtzman, D. M. (2001) · Neurochemistry International · doi:10.1016/s0197-0186(01)00049-3 · Cited by 180 · see citing works
Loughrey, D., & Dahlman, J. E. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00601 · Cited by 173 · see citing works
Apolipoprotein E and cholesterol in aging and disease in the brain
de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.505 · Cited by 164 · see citing works
Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)
Ramkumar, H. L., Zhang, J., & Chan, C.-C. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2010.02.002 · Cited by 163 · see citing works
ATP-binding cassette transporter A1: From metabolism to neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.007 · Cited by 144 · see citing works
Grehan, S., Tse, E., & Taylor, J. M. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-03-00812.2001 · Cited by 138 · see citing works
Lipids in the nervous system: From biochemistry and molecular biology to patho-physiology
Cermenati, G., Mitro, N., Audano, M., Melcangi, R. C., Crestani, M., De Fabiani, E., & Caruso, D. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.08.011 · Cited by 137 · see citing works
Ji, Z.-S., Pitas, R. E., & Mahley, R. W. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13452 · Cited by 134 · see citing works
Self-citationNakamura, T., Watanabe, A., Fujino, T., Hosono, T., & Michikawa, M. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-35 · Cited by 124 · see citing works
DeMattos, R. B., Curtiss, L. K., & Williams, D. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.7.4206 · Cited by 123 · see citing works
Fagan, A. M., Murphy, B. A., Patel, S. N., Kilbridge, J. F., Mobley, W. C., Bu, G., & Holtzman, D. M. (1998) · Experimental Neurology · doi:10.1006/exnr.1998.6818 · Cited by 116 · see citing works
Cholesterol synthesis rate in human hippocampus declines with aging
Thelen, K. M., Falkai, P., Bayer, T. A., & Lütjohann, D. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.04.034 · Cited by 107 · see citing works
Minagawa, H., Gong, J., Jung, C., Watanabe, A., Lund‐Katz, S., Phillips, M. C., Saito, H., & Michikawa, M. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22073 · Cited by 90 · see citing works
Kaiser, K., Gyllborg, D., Procházka, J., Salašová, A., Kompaníková, P., Molina, F. L., Laguna-Goya, R., Radaszkiewicz, T., Harnoš, J., Procházková, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09298-4 · Cited by 87 · see citing works
Mulder, M., Blokland, A., van den Berg, D.-J., Schulten, H., Bakker, A. H. F., Terwel, D., Honig, W., de Kloet, E. R., Havekes, L. M., Steinbusch, H. W. M., et al. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780307 · Cited by 74 · see citing works
Shanmugaratnam, J., Berg, E., Kimerer, L., Johnson, R. J., Amaratunga, A., Schreiber, B. M., & Fine, R. E. (1997) · Molecular Brain Research · doi:10.1016/s0169-328x(97)00176-9 · Cited by 68 · see citing works
The generation and function of soluble apoE receptors in the CNS
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
Hirsch-Reinshagen, V., & Wellington, C. L. (2007) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32813aeabf · Cited by 61 · see citing works
Apolipoprotein E as a β-amyloid-independent factor in Alzheimer’s disease
Wolf, A. B., Valla, J., Bu, G., Kim, J., LaDu, M., Reiman, E. M., & Caselli, R. J. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt204 · Cited by 55 · see citing works
Fagan, A. M., Christopher, E., Taylor, J. W., Parsadanian, M., Spinner, M., Watson, M., Fryer, J. D., Wahrle, S., Bales, K. R., Paul, S. M., et al. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63399-8 · Cited by 54 · see citing works
Choi, J., Gao, J., Kim, J., Hong, C., Kim, J., & Tontonoz, P. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aad1904 · Cited by 49 · 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
Structural Analysis of Lipoprotein E Particles
Schneeweis, L. A., Koppaka, V., Lund-Katz, S., Phillips, M. C., & Axelsen, P. H. (2005) · Biochemistry · doi:10.1021/bi050872j · Cited by 39 · see citing works
Differential effects of apoE4 and activation of ABCA1 on brain and plasma lipoproteins
Boehm-Cagan, A., Bar, R., Harats, D., Shaish, A., Levkovitz, H., Bielicki, J. K., Johansson, J. O., & Michaelson, D. M. (2016) · PLOS ONE · doi:10.1371/journal.pone.0166195 · Cited by 29 · see citing works
Merrill, N. J., Davidson, W. S., He, Y., Díaz Ludovico, I., Sarkar, S., Berger, M. R., McDermott, J. E., Van Eldik, L. J., Wilcock, D. M., Monroe, M. E., et al. (2023) · Science Advances · doi:10.1126/sciadv.adi5571 · Cited by 27 · see citing works
High-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
Pedrini, S., Chatterjee, P., Hone, E., & Martins, R. N. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15170 · Cited by 22 · see citing works
MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease
Yoon, H., Flores, L. F., & Kim, J. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.04.020 · Cited by 23 · see citing works
“APOE in the brain has a slightly higher molecular weight and has more acidic isoforms [41].”
Background
- Authors
- Pitas, R. E., Boyles, J. K., Lee, S. H., Hui, D., & Weisgraber, K. H.
- Affiliations
- University of California, San Francisco (US)
- ORCID
- Hui, D
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1987-10
- Volume
- 262
- Issue
- 29
- Pages
- 14352-14360
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1963021413
- Cited by
- 714
- References
- 5
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 13 · 2023: 17 · 2022: 16 · 2021: 14 · 2020: 17 · 2019: 22 · 2018: 11 · 2017: 15 · 2016: 14 · 2015: 20 · 2014: 28 · 2013: 17 · 2012: 13
- FWCI
- 12.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, apolipoprotein A-I, brain cholesterol homeostasis, lipid transport, astrocytes, arachnoid cells, lipoprotein density, sialylation, HDL binding
- MeSH terms
- Adult, Animals, Apolipoproteins E, Brain, Callitrichinae, Cerebrospinal Fluid Proteins, Cholesterol, Dogs, Humans, Immunohistochemistry, Lipoproteins, Receptors, LDL, Species Specificity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
