• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Jul 1988; 82(1): 177–188.
PMCID: PMC303492

Immunohistochemical localization of apolipoprotein E in human glial neoplasms.


Immunocytochemical analyses revealed the presence and distribution of apolipoprotein E (apo E) in normal human brain tissue as well as in 77 human intracranial neoplasms. In normal brain tissues, the perikarya of astrocytes exhibited a strong positive reaction, whereas the Bergmann glia were stained to a moderate degree. However, no immunoreactivity was observed with neurons, oligodendrocytes, ependymal cells, and choroidal epithelium. Among the intracranial neoplasms, oligodendroglioma, choroid plexus papilloma, hemangioblastoma, primary malignant lymphoma, neurinoma, meningioma, pituitary adenoma, and craniopharyngioma were all negative. Immunoreactivity in the peripheral neuroblastoma was nil. However, the perikarya of astrocytomas and glioblastomas showed a positive reaction. Analyses on the degree of anaplasia and the amount of apo-E as an intensity of immunostaining showed a negative correlation. The astrocytic elements were stained in mixed oligoastrocytomas and medulloblastomas with glial differentiation. A few cases of ependymomas showed weak perikaryal immunostaining. Western blot analyses with anti-apo E antibody of a freshly prepared surgical specimen with astrocytomas revealed a single band with a molecular weight of approximately 37,000. The well differentiated cultured human astrocytoma cells secreted apo E into the medium. These lines of evidence suggest that apo E may serve as a potential marker specific for astrocytomas and glioblastomas, as well as an indicator of astrocytic tumor cell differentiation. The apo E localization in human brain tumors could be clinically relevant and diagnostically useful.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (5.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Rall SC, Jr, Weisgraber KH, Mahley RW. Human apolipoprotein E. The complete amino acid sequence. J Biol Chem. 1982 Apr 25;257(8):4171–4178. [PubMed]
  • Mahley RW, Innerarity TL. Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta. 1983 May 24;737(2):197–222. [PubMed]
  • Mahley RW, Innerarity TL, Rall SC, Jr, Weisgraber KH. Plasma lipoproteins: apolipoprotein structure and function. J Lipid Res. 1984 Dec 1;25(12):1277–1294. [PubMed]
  • Pitas RE, Innerarity TL, Arnold KS, Mahley RW. Rate and equilibrium constants for binding of apo-E HDLc (a cholesterol-induced lipoprotein) and low density lipoproteins to human fibroblasts: evidence for multiple receptor binding of apo-E HDLc. Proc Natl Acad Sci U S A. 1979 May;76(5):2311–2315. [PMC free article] [PubMed]
  • Hui DY, Innerarity TL, Mahley RW. Lipoprotein binding to canine hepatic membranes. Metabolically distinct apo-E and apo-B,E receptors. J Biol Chem. 1981 Jun 10;256(11):5646–5655. [PubMed]
  • Carrella M, Cooper AD. High affinity binding of chylomicron remnants to rat liver plasma membranes. Proc Natl Acad Sci U S A. 1979 Jan;76(1):338–342. [PMC free article] [PubMed]
  • Williams DL, Dawson PA, Newman TC, Rudel LL. Apolipoprotein E synthesis in peripheral tissues of nonhuman primates. J Biol Chem. 1985 Feb 25;260(4):2444–2451. [PubMed]
  • Blue ML, Williams DL, Zucker S, Khan SA, Blum CB. Apolipoprotein E synthesis in human kidney, adrenal gland, and liver. Proc Natl Acad Sci U S A. 1983 Jan;80(1):283–287. [PMC free article] [PubMed]
  • Elshourbagy NA, Liao WS, Mahley RW, Taylor JM. Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. Proc Natl Acad Sci U S A. 1985 Jan;82(1):203–207. [PMC free article] [PubMed]
  • Roheim PS, Carey M, Forte T, Vega GL. Apolipoproteins in human cerebrospinal fluid. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4646–4649. [PMC free article] [PubMed]
  • Boyles JK, Pitas RE, Wilson E, Mahley RW, Taylor JM. Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J Clin Invest. 1985 Oct;76(4):1501–1513. [PMC free article] [PubMed]
  • Gebicke-Haerter PJ, Darby JK, Shooter EM, Riccardi VM, Weisgraber KH, Boyles JK, Mahley RW. Apolipoprotein E synthesis in neurofibrosarcoma and schwannoma cell cultures from two individuals with neurofibromatosis. Exp Neurol. 1987 Feb;95(2):323–335. [PubMed]
  • Shelburne FA, Quarfordt SH. The interaction of heparin with an apoprotein of human very low density lipoprotein. J Clin Invest. 1977 Oct;60(4):944–950. [PMC free article] [PubMed]
  • Murakami M, Horiuchi S, Takata K, Morino Y. Scavenger receptor for malondialdehyde-modified high density lipoprotein on rat sinusoidal liver cells. Biochem Biophys Res Commun. 1986 May 29;137(1):29–35. [PubMed]
  • Murakami M, Horiuchi S, Takata K, Morino Y. Distinction in the mode of receptor-mediated endocytosis between high density lipoprotein and acetylated high density lipoprotein: evidence for high density lipoprotein receptor-mediated cholesterol transfer. J Biochem. 1987 Mar;101(3):729–741. [PubMed]
  • Horiuchi S, Takata K, Morino Y. Characterization of a membrane-associated receptor from rat sinusoidal liver cells that binds formaldehyde-treated serum albumin. J Biol Chem. 1985 Jan 10;260(1):475–481. [PubMed]
  • Horiuchi S, Murakami M, Takata K, Morino Y. Scavenger receptor for aldehyde-modified proteins. J Biol Chem. 1986 Apr 15;261(11):4962–4966. [PubMed]
  • Ohta T, Fidge NH, Nestel PJ. Studies on the in vivo and in vitro distribution of apolipoprotein A-IV in human plasma and lymph. J Clin Invest. 1985 Sep;76(3):1252–1260. [PMC free article] [PubMed]
  • Yoshitake S, Imagawa M, Ishikawa E, Niitsu Y, Urushizaki I, Nishiura M, Kanazawa R, Kurosaki H, Tachibana S, Nakazawa N, et al. Mild and efficient conjugation of rabbit Fab' and horseradish peroxidase using a maleimide compound and its use for enzyme immunoassay. J Biochem. 1982 Nov;92(5):1413–1424. [PubMed]
  • Fukuda S, Horiuchi S, Tomita K, Murakami M, Morino Y, Takahashi K. Acetylated low-density lipoprotein is endocytosed through coated pits by rat peritoneal macrophages. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;52(1):1–13. [PubMed]
  • Kyhse-Andersen J. Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods. 1984 Dec;10(3-4):203–209. [PubMed]
  • Salm AK, Hatton GI, Nilaver G. Immunoreactive glial fibrillary acidic protein in pituicytes of the rat neurohypophysis. Brain Res. 1982 Mar 25;236(2):471–476. [PubMed]
  • Bascó E, Woodhams PL, Hajós F, Balázs R. Immunocytochemical demonstration of glial fibrillary acidic protein in mouse tanycytes. Anat Embryol (Berl) 1981;162(2):217–222. [PubMed]
  • Bignami A, Eng LF, Dahl D, Uyeda CT. Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res. 1972 Aug 25;43(2):429–435. [PubMed]
  • Velasco ME, Dahl D, Roessmann U, Gambetti P. Immunohistochemical localization of glial fibrillary acidic protein in human glial neoplasms. Cancer. 1980 Feb;45(3):484–494. [PubMed]
  • Brooks DA, Zola H, McNamara PJ, Bradley J, Bradstock KF, Hancock WW, Atkins RC. Membrane antigens of human cells of the monocyte/macrophage lineage studied with monoclonal antibodies. Pathology. 1983 Jan;15(1):45–52. [PubMed]
  • Müller HW, Ignatius MJ, Hangen DH, Shooter EM. Expression of specific sheath cell proteins during peripheral nerve growth and regeneration in mammals. J Cell Biol. 1986 Feb;102(2):393–402. [PMC free article] [PubMed]
  • Snipes GJ, McGuire CB, Norden JJ, Freeman JA. Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1130–1134. [PMC free article] [PubMed]
  • Ignatius MJ, Gebicke-Härter PJ, Skene JH, Schilling JW, Weisgraber KH, Mahley RW, Shooter EM. Expression of apolipoprotein E during nerve degeneration and regeneration. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1125–1129. [PMC free article] [PubMed]
  • Müller HW, Gebicke-Härter PJ, Hangen DH, Shooter EM. A specific 37,000-dalton protein that accumulates in regenerating but not in nonregenerating mammalian nerves. Science. 1985 Apr 26;228(4698):499–501. [PubMed]
  • Basu SK, Ho YK, Brown MS, Bilheimer DW, Anderson RG, Goldstein JL. Biochemical and genetic studies of the apoprotein E secreted by mouse macrophages and human monocytes. J Biol Chem. 1982 Aug 25;257(16):9788–9795. [PubMed]
  • Zannis VI, McPherson J, Goldberger G, Karathanasis SK, Breslow JL. Synthesis, intracellular processing, and signal peptide of human apolipoprotein E. J Biol Chem. 1984 May 10;259(9):5495–5499. [PubMed]
  • Albrechtsen M, von Gerstenberg AC, Bock E. Mouse monoclonal antibodies reacting with human brain glial fibrillary acidic protein. J Neurochem. 1984 Jan;42(1):86–93. [PubMed]
  • Courel MN, Girard N, Delpech B, Chauzy C. Specific monoclonal antibodies to glial fibrillary acidic protein (GFAP). J Neuroimmunol. 1986 Jun;11(4):271–276. [PubMed]
  • Ludwin SK, Kosek JC, Eng LF. The topographical distribution of S-100 and GFA proteins in the adult rat brain: an immunohistochemical study using horseradish peroxidase-labelled antibodies. J Comp Neurol. 1976 Jan 15;165(2):197–207. [PubMed]
  • de Armond SJ, Eng LF, Rubinstein LJ. The application of glial fibrillary acidic (GFA) protein immunohistochemistry in neurooncology. A progress report. Pathol Res Pract. 1980;168(4):374–394. [PubMed]
  • Herpers MJ, Budka H. Glial fibrillary acidic protein (GFAP) in oligodendroglial tumors: gliofibrillary oligodendroglioma and transitional oligoastrocytoma as subtypes of oligodendroglioma. Acta Neuropathol. 1984;64(4):265–272. [PubMed]
  • Wilkinson IM, Anderson JR, Holmes AE. Oligodendroglioma: an analysis of 42 cases. J Neurol Neurosurg Psychiatry. 1987 Mar;50(3):304–312. [PMC free article] [PubMed]
  • Gullotta F, Schindler F, Schmutzler R, Weeks-Seifert A. GFAP in brain tumor diagnosis: possibilities and limitations. Pathol Res Pract. 1985 Jul;180(1):54–60. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...