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. 1994 Jun;144(6):1183–1187.

Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys.

A Poduri 1, M Gearing 1, G W Rebeck 1, S S Mirra 1, J Tigges 1, B T Hyman 1
PMCID: PMC1887468  PMID: 8203459

Abstract

Recent studies of late onset familial and sporadic Alzheimer's disease (AD) show a genetic disequilibrium between inheritance of the epsilon 4 allele of the apolipoprotein E (ApoE) gene and development of AD. beta-Amyloid (A beta)-positive senile plaques and blood vessels in AD are immunoreactive for ApoE, suggesting that ApoE plays a role in amyloid deposition. We examined the brains of nine rhesus monkeys (Macaca mulatta) to determine the immunohistochemical distribution of ApoE and to investigate the association of ApoE with A beta in this species. Antibodies to ApoE and A beta labeled senile plaques and vessels in the brains of aged monkeys, indicating cross-species homogeneity of the association of these two proteins. Polymerase chain reaction/restriction enzyme analysis of the ApoE epsilon 3/epsilon 4 allelic site (residue 112) in the rhesus monkey revealed that the rhesus has an arginine at this site like the human epsilon 4 allele, the cynomolgus monkey, baboon, cow, pig, mouse, and rat but unlike the human epsilon 3 allele and the rabbit. These results emphasize the value of aged nonhuman primates as animal models for A beta deposition and ApoE4-A beta interactions in AD and aging.

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Selected References

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  1. Brzozowska A., Fries R., Womack J. E., Grimholt U., Myklebost O., Rogne S. Isolation, sequencing, and expression analysis of a bovine apolipoprotein E (APOE) cDNA and chromosomal localization of the APOE locus. Mamm Genome. 1993;4(1):53–57. doi: 10.1007/BF00364665. [DOI] [PubMed] [Google Scholar]
  2. Cork L. C., Masters C., Beyreuther K., Price D. L. Development of senile plaques. Relationships of neuronal abnormalities and amyloid deposits. Am J Pathol. 1990 Dec;137(6):1383–1392. [PMC free article] [PubMed] [Google Scholar]
  3. Hao Q. L., Yamin T. T., Pan T. C., Chen S. L., Chen B. S., Kroon P. A., Chao Y. S. Isolation and characterization of a full-length rabbit apolipoprotein E cDNA. Atherosclerosis. 1987 Jul;66(1-2):125–130. doi: 10.1016/0021-9150(87)90187-0. [DOI] [PubMed] [Google Scholar]
  4. Hixson J. E., Cox L. A., Borenstein S. The baboon apolipoprotein E gene: structure, expression, and linkage with the gene for apolipoprotein C-1. Genomics. 1988 May;2(4):315–323. doi: 10.1016/0888-7543(88)90020-1. [DOI] [PubMed] [Google Scholar]
  5. Hixson J. E., Vernier D. T. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990 Mar;31(3):545–548. [PubMed] [Google Scholar]
  6. 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]
  7. Mahley R. W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988 Apr 29;240(4852):622–630. doi: 10.1126/science.3283935. [DOI] [PubMed] [Google Scholar]
  8. Marotti K. R., Whitted B. E., Castle C. K., Polites H. G., Melchior G. W. Nucleotide sequence of the cynomolgus monkey apolipoprotein E cDNA. Nucleic Acids Res. 1989 Feb 25;17(4):1778–1778. doi: 10.1093/nar/17.4.1778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mayeux R., Stern Y., Ottman R., Tatemichi T. K., Tang M. X., Maestre G., Ngai C., Tycko B., Ginsberg H. The apolipoprotein epsilon 4 allele in patients with Alzheimer's disease. Ann Neurol. 1993 Nov;34(5):752–754. doi: 10.1002/ana.410340527. [DOI] [PubMed] [Google Scholar]
  10. McLean J. W., Elshourbagy N. A., Chang D. J., Mahley R. W., Taylor J. M. Human apolipoprotein E mRNA. cDNA cloning and nucleotide sequencing of a new variant. J Biol Chem. 1984 May 25;259(10):6498–6504. [PubMed] [Google Scholar]
  11. McLean J. W., Fukazawa C., Taylor J. M. Rat apolipoprotein E mRNA. Cloning and sequencing of double-stranded cDNA. J Biol Chem. 1983 Jul 25;258(14):8993–9000. [PubMed] [Google Scholar]
  12. Namba Y., Tomonaga M., Kawasaki H., Otomo E., Ikeda K. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease. Brain Res. 1991 Feb 8;541(1):163–166. doi: 10.1016/0006-8993(91)91092-f. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Poirier J., Hess M., May P. C., Finch C. E. Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning. Brain Res Mol Brain Res. 1991 Sep;11(2):97–106. doi: 10.1016/0169-328x(91)90111-a. [DOI] [PubMed] [Google Scholar]
  15. Price D. L., Martin L. J., Sisodia S. S., Walker L. C., Cork L. C. Alzheimer's disease-type brain abnormalities in animal models. Prog Clin Biol Res. 1992;379:271–287. [PubMed] [Google Scholar]
  16. Rajavashisth T. B., Kaptein J. S., Reue K. L., Lusis A. J. Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8085–8089. doi: 10.1073/pnas.82.23.8085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Saunders A. M., Strittmatter W. J., Schmechel D., George-Hyslop P. H., Pericak-Vance M. A., Joo S. H., Rosi B. L., Gusella J. F., Crapper-MacLachlan D. R., Alberts M. J. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1993 Aug;43(8):1467–1472. doi: 10.1212/wnl.43.8.1467. [DOI] [PubMed] [Google Scholar]
  19. Schmechel D. E., Saunders A. M., Strittmatter W. J., Crain B. J., Hulette C. M., Joo S. H., Pericak-Vance M. A., Goldgaber D., Roses A. D. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9649–9653. doi: 10.1073/pnas.90.20.9649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Selkoe D. J., Bell D. S., Podlisny M. B., Price D. L., Cork L. C. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science. 1987 Feb 20;235(4791):873–877. doi: 10.1126/science.3544219. [DOI] [PubMed] [Google Scholar]
  21. Strittmatter W. J., Saunders A. M., Schmechel D., Pericak-Vance M., Enghild J., Salvesen G. S., Roses A. D. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977–1981. doi: 10.1073/pnas.90.5.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Strittmatter W. J., Weisgraber K. H., Goedert M., Saunders A. M., Huang D., Corder E. H., Dong L. M., Jakes R., Alberts M. J., Gilbert J. R. Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Exp Neurol. 1994 Feb;125(2):163–174. doi: 10.1006/exnr.1994.1019. [DOI] [PubMed] [Google Scholar]
  23. Wisniewski T., Frangione B. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci Lett. 1992 Feb 3;135(2):235–238. doi: 10.1016/0304-3940(92)90444-c. [DOI] [PubMed] [Google Scholar]
  24. Zannis V. I., Nicolosi R. J., Jensen E., Breslow J. L., Hayes K. C. Plasma and hepatic apoE isoproteins of nonhuman primates. Differences in apoE among humans, apes, and New and Old World monkeys. J Lipid Res. 1985 Dec;26(12):1421–1430. [PubMed] [Google Scholar]

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