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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Feb;148(2):399–403.

Expression of the macrophage scavenger receptor, a multifunctional lipoprotein receptor, in microglia associated with senile plaques in Alzheimer's disease.

R H Christie 1, M Freeman 1, B T Hyman 1
PMCID: PMC1861668  PMID: 8579103

Abstract

The macrophage scavenger receptor is a multifunctional receptor whose ligands include oxidized low density lipoprotein (LDL), as well as several other polyanionic macromolecules. Although the capacity of the receptor to bind modified LDL has implicated it in the process of atherosclerosis, its physiological role remains uncertain. We have examined human brain for expression of macrophage scavenger receptor as part of ongoing studies of lipoprotein receptors in the central nervous system. The receptor is expressed on microglia, but not on astrocytes, neurons, or vessel-associated structures. In Alzheimer disease, there is strong expression of the scavenger receptor in association with senile plaques.

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  1. Acton S., Resnick D., Freeman M., Ekkel Y., Ashkenas J., Krieger M. The collagenous domains of macrophage scavenger receptors and complement component C1q mediate their similar, but not identical, binding specificities for polyanionic ligands. J Biol Chem. 1993 Feb 15;268(5):3530–3537. [PubMed] [Google Scholar]
  2. Anwar N., Lovestone S., Cheetham M. E., Levy R., Powell J. F. Apolipoprotein E-epsilon 4 allele and Alzheimer's disease. Lancet. 1993 Nov 20;342(8882):1308–1309. doi: 10.1016/0140-6736(93)92404-h. [DOI] [PubMed] [Google Scholar]
  3. Araki N., Higashi T., Mori T., Shibayama R., Kawabe Y., Kodama T., Takahashi K., Shichiri M., Horiuchi S. Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction. Eur J Biochem. 1995 Jun 1;230(2):408–415. doi: 10.1111/j.1432-1033.1995.0408h.x. [DOI] [PubMed] [Google Scholar]
  4. Beisiegel U., Weber W., Ihrke G., Herz J., Stanley K. K. The LDL-receptor-related protein, LRP, is an apolipoprotein E-binding protein. Nature. 1989 Sep 14;341(6238):162–164. doi: 10.1038/341162a0. [DOI] [PubMed] [Google Scholar]
  5. Brown M. S., Goldstein J. L. Atherosclerosis. Scavenging for receptors. Nature. 1990 Feb 8;343(6258):508–509. doi: 10.1038/343508a0. [DOI] [PubMed] [Google Scholar]
  6. Brown M. S., Goldstein J. L., Krieger M., Ho Y. K., Anderson R. G. Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. J Cell Biol. 1979 Sep;82(3):597–613. doi: 10.1083/jcb.82.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Corder E. H., Saunders A. M., Strittmatter W. J., Schmechel D. E., Gaskell P. C., Small G. W., Roses A. D., Haines J. L., Pericak-Vance M. A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993 Aug 13;261(5123):921–923. doi: 10.1126/science.8346443. [DOI] [PubMed] [Google Scholar]
  8. Doi T., Higashino K., Kurihara Y., Wada Y., Miyazaki T., Nakamura H., Uesugi S., Imanishi T., Kawabe Y., Itakura H. Charged collagen structure mediates the recognition of negatively charged macromolecules by macrophage scavenger receptors. J Biol Chem. 1993 Jan 25;268(3):2126–2133. [PubMed] [Google Scholar]
  9. Goldstein J. L., Ho Y. K., Basu S. K., Brown M. S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A. 1979 Jan;76(1):333–337. doi: 10.1073/pnas.76.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hyman B. T., Tanzi R. E., Marzloff K., Barbour R., Schenk D. Kunitz protease inhibitor-containing amyloid beta protein precursor immunoreactivity in Alzheimer's disease. J Neuropathol Exp Neurol. 1992 Jan;51(1):76–83. doi: 10.1097/00005072-199201000-00009. [DOI] [PubMed] [Google Scholar]
  11. Khachaturian Z. S. Diagnosis of Alzheimer's disease. Arch Neurol. 1985 Nov;42(11):1097–1105. doi: 10.1001/archneur.1985.04060100083029. [DOI] [PubMed] [Google Scholar]
  12. Kodama T., Reddy P., Kishimoto C., Krieger M. Purification and characterization of a bovine acetyl low density lipoprotein receptor. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9238–9242. doi: 10.1073/pnas.85.23.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kowal R. C., Herz J., Goldstein J. L., Esser V., Brown M. S. Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5810–5814. doi: 10.1073/pnas.86.15.5810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krieger M., Herz J. Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Annu Rev Biochem. 1994;63:601–637. doi: 10.1146/annurev.bi.63.070194.003125. [DOI] [PubMed] [Google Scholar]
  15. Krieger M. Molecular flypaper and atherosclerosis: structure of the macrophage scavenger receptor. Trends Biochem Sci. 1992 Apr;17(4):141–146. doi: 10.1016/0968-0004(92)90322-z. [DOI] [PubMed] [Google Scholar]
  16. Li H., Freeman M. W., Libby P. Regulation of smooth muscle cell scavenger receptor expression in vivo by atherogenic diets and in vitro by cytokines. J Clin Invest. 1995 Jan;95(1):122–133. doi: 10.1172/JCI117628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liddell M., Williams J., Bayer A., Kaiser F., Owen M. Confirmation of association between the e4 allele of apolipoprotein E and Alzheimer's disease. J Med Genet. 1994 Mar;31(3):197–200. doi: 10.1136/jmg.31.3.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matsumoto A., Naito M., Itakura H., Ikemoto S., Asaoka H., Hayakawa I., Kanamori H., Aburatani H., Takaku F., Suzuki H. Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9133–9137. doi: 10.1073/pnas.87.23.9133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mirra S. S., Heyman A., McKeel D., Sumi S. M., Crain B. J., Brownlee L. M., Vogel F. S., Hughes J. P., van Belle G., Berg L. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991 Apr;41(4):479–486. doi: 10.1212/wnl.41.4.479. [DOI] [PubMed] [Google Scholar]
  20. Naito M., Suzuki H., Mori T., Matsumoto A., Kodama T., Takahashi K. Coexpression of type I and type II human macrophage scavenger receptors in macrophages of various organs and foam cells in atherosclerotic lesions. Am J Pathol. 1992 Sep;141(3):591–599. [PMC free article] [PubMed] [Google Scholar]
  21. Poirier J., Davignon J., Bouthillier D., Kogan S., Bertrand P., Gauthier S. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet. 1993 Sep 18;342(8873):697–699. doi: 10.1016/0140-6736(93)91705-q. [DOI] [PubMed] [Google Scholar]
  22. Rebeck G. W., Harr S. D., Strickland D. K., Hyman B. T. Multiple, diverse senile plaque-associated proteins are ligands of an apolipoprotein E receptor, the alpha 2-macroglobulin receptor/low-density-lipoprotein receptor-related protein. Ann Neurol. 1995 Feb;37(2):211–217. doi: 10.1002/ana.410370212. [DOI] [PubMed] [Google Scholar]
  23. Rebeck G. W., Perls T. T., West H. L., Sodhi P., Lipsitz L. A., Hyman B. T. Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer's patients and cognitively normal individuals. Neurology. 1994 Aug;44(8):1513–1516. doi: 10.1212/wnl.44.8.1513. [DOI] [PubMed] [Google Scholar]
  24. Rebeck G. W., Reiter J. S., Strickland D. K., Hyman B. T. Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions. Neuron. 1993 Oct;11(4):575–580. doi: 10.1016/0896-6273(93)90070-8. [DOI] [PubMed] [Google Scholar]
  25. Smith M. A., Taneda S., Richey P. L., Miyata S., Yan S. D., Stern D., Sayre L. M., Monnier V. M., Perry G. Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5710–5714. doi: 10.1073/pnas.91.12.5710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tsai M. S., Tangalos E. G., Petersen R. C., Smith G. E., Schaid D. J., Kokmen E., Ivnik R. J., Thibodeau S. N. Apolipoprotein E: risk factor for Alzheimer disease. Am J Hum Genet. 1994 Apr;54(4):643–649. [PMC free article] [PubMed] [Google Scholar]
  27. Vitek M. P., Bhattacharya K., Glendening J. M., Stopa E., Vlassara H., Bucala R., Manogue K., Cerami A. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4766–4770. doi: 10.1073/pnas.91.11.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]

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