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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Aug;145(2):452–460.

High tissue content of soluble beta 1-40 is linked to cerebral amyloid angiopathy.

N Suzuki 1, T Iwatsubo 1, A Odaka 1, Y Ishibashi 1, C Kitada 1, Y Ihara 1
PMCID: PMC1887395  PMID: 8053502

Abstract

We developed two highly sensitive enzyme immunoassays for beta-protein with different specificities. One is specific for beta 1-40, while the other is equally sensitive to beta 1-38, beta 1-39, beta 1-40, and beta 1-42. With the enzyme immunoassays we investigated whether the soluble fraction from brain tissue contains beta 1-40 or other species of beta-protein. Aged control and Alzheimer's diseased brains showed highly variable values of beta 1-40, which was found to be the major beta species in their extracts. High tissue content of soluble beta 1-40 was not correlated to the abundance of senile plaques but was invariably associated with cerebral amyloid angiopathy. Thus, the tissue level of soluble beta 1-40 should be useful for the quantification of cerebral amyloid angiopathy.

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Selected References

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  1. Coria F., Castaño E. M., Frangione B. Brain amyloid in normal aging and cerebral amyloid angiopathy is antigenically related to Alzheimer's disease beta-protein. Am J Pathol. 1987 Dec;129(3):422–428. [PMC free article] [PubMed] [Google Scholar]
  2. Goate A., Chartier-Harlin M. C., Mullan M., Brown J., Crawford F., Fidani L., Giuffra L., Haynes A., Irving N., James L. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991 Feb 21;349(6311):704–706. doi: 10.1038/349704a0. [DOI] [PubMed] [Google Scholar]
  3. Haass C., Schlossmacher M. G., Hung A. Y., Vigo-Pelfrey C., Mellon A., Ostaszewski B. L., Lieberburg I., Koo E. H., Schenk D., Teplow D. B. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature. 1992 Sep 24;359(6393):322–325. doi: 10.1038/359322a0. [DOI] [PubMed] [Google Scholar]
  4. Ichimori Y., Suzuki N., Kitada C., Tsukamoto K. Monoclonal antibodies to human interferon-gamma. II: Antibodies with neutralizing activity. Hybridoma. 1987 Apr;6(2):173–181. doi: 10.1089/hyb.1987.6.173. [DOI] [PubMed] [Google Scholar]
  5. Jarrett J. T., Lansbury P. T., Jr Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell. 1993 Jun 18;73(6):1055–1058. doi: 10.1016/0092-8674(93)90635-4. [DOI] [PubMed] [Google Scholar]
  6. Joachim C. L., Duffy L. K., Morris J. H., Selkoe D. J. Protein chemical and immunocytochemical studies of meningovascular beta-amyloid protein in Alzheimer's disease and normal aging. Brain Res. 1988 Nov 22;474(1):100–111. doi: 10.1016/0006-8993(88)90673-7. [DOI] [PubMed] [Google Scholar]
  7. Kanemaru K., Hasegawa M., Shimada H., Ihara Y. The presence of a novel protein in calf serum that recognizes beta amyloid in the formalin-fixed section. Am J Pathol. 1990 Sep;137(3):677–687. [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Kitamoto T., Ogomori K., Tateishi J., Prusiner S. B. Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Lab Invest. 1987 Aug;57(2):230–236. [PubMed] [Google Scholar]
  10. Kondo J., Honda T., Mori H., Hamada Y., Miura R., Ogawara M., Ihara Y. The carboxyl third of tau is tightly bound to paired helical filaments. Neuron. 1988 Nov;1(9):827–834. doi: 10.1016/0896-6273(88)90130-4. [DOI] [PubMed] [Google Scholar]
  11. Maggio J. E., Stimson E. R., Ghilardi J. R., Allen C. J., Dahl C. E., Whitcomb D. C., Vigna S. R., Vinters H. V., Labenski M. E., Mantyh P. W. Reversible in vitro growth of Alzheimer disease beta-amyloid plaques by deposition of labeled amyloid peptide. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5462–5466. doi: 10.1073/pnas.89.12.5462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mandybur T. I. The incidence of cerebral amyloid angiopathy in Alzheimer's disease. Neurology. 1975 Feb;25(2):120–126. doi: 10.1212/wnl.25.2.120. [DOI] [PubMed] [Google Scholar]
  13. Mann D. M., Esiri M. M. The site of the earliest lesions of Alzheimer's disease. N Engl J Med. 1988 Mar 24;318(12):789–790. doi: 10.1056/NEJM198803243181218. [DOI] [PubMed] [Google Scholar]
  14. Maruyama K., Ikeda S., Ishihara T., Allsop D., Yanagisawa N. Immunohistochemical characterization of cerebrovascular amyloid in 46 autopsied cases using antibodies to beta protein and cystatin C. Stroke. 1990 Mar;21(3):397–403. doi: 10.1161/01.str.21.3.397. [DOI] [PubMed] [Google Scholar]
  15. Masters C. L., Simms G., Weinman N. A., Multhaup G., McDonald B. L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245–4249. doi: 10.1073/pnas.82.12.4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mori H., Takio K., Ogawara M., Selkoe D. J. Mass spectrometry of purified amyloid beta protein in Alzheimer's disease. J Biol Chem. 1992 Aug 25;267(24):17082–17086. [PubMed] [Google Scholar]
  17. Mullan M., Crawford F. Genetic and molecular advances in Alzheimer's disease. Trends Neurosci. 1993 Oct;16(10):398–403. doi: 10.1016/0166-2236(93)90007-9. [DOI] [PubMed] [Google Scholar]
  18. Naruse S., Igarashi S., Kobayashi H., Aoki K., Inuzuka T., Kaneko K., Shimizu T., Iihara K., Kojima T., Miyatake T. Mis-sense mutation Val----Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet. 1991 Apr 20;337(8747):978–979. doi: 10.1016/0140-6736(91)91612-x. [DOI] [PubMed] [Google Scholar]
  19. Prelli F., Castaño E., Glenner G. G., Frangione B. Differences between vascular and plaque core amyloid in Alzheimer's disease. J Neurochem. 1988 Aug;51(2):648–651. doi: 10.1111/j.1471-4159.1988.tb01087.x. [DOI] [PubMed] [Google Scholar]
  20. Roher A. E., Lowenson J. D., Clarke S., Wolkow C., Wang R., Cotter R. J., Reardon I. M., Zürcher-Neely H. A., Heinrikson R. L., Ball M. J. Structural alterations in the peptide backbone of beta-amyloid core protein may account for its deposition and stability in Alzheimer's disease. J Biol Chem. 1993 Feb 15;268(5):3072–3083. [PubMed] [Google Scholar]
  21. Roher A. E., Lowenson J. D., Clarke S., Woods A. S., Cotter R. J., Gowing E., Ball M. J. beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10836–10840. doi: 10.1073/pnas.90.22.10836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Selkoe D. J. The molecular pathology of Alzheimer's disease. Neuron. 1991 Apr;6(4):487–498. doi: 10.1016/0896-6273(91)90052-2. [DOI] [PubMed] [Google Scholar]
  23. Seubert P., Vigo-Pelfrey C., Esch F., Lee M., Dovey H., Davis D., Sinha S., Schlossmacher M., Whaley J., Swindlehurst C. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature. 1992 Sep 24;359(6393):325–327. doi: 10.1038/359325a0. [DOI] [PubMed] [Google Scholar]
  24. Shoji M., Golde T. E., Ghiso J., Cheung T. T., Estus S., Shaffer L. M., Cai X. D., McKay D. M., Tintner R., Frangione B. Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science. 1992 Oct 2;258(5079):126–129. doi: 10.1126/science.1439760. [DOI] [PubMed] [Google Scholar]
  25. Suzuki N., Harada M., Kitada C., Ohkubo S., Matsumoto H., Watanabe T., Coy D. H., Tsuda M., Arimura A., Fujino M. Production of immunoreactive pituitary adenylate cyclase activating polypeptide (PACAP) by human neuroblastoma cells, IMR-32: detection and characterization with monoclonal and polyclonal antibodies against different epitopes of PACAP. J Biochem. 1993 May;113(5):549–556. doi: 10.1093/oxfordjournals.jbchem.a124081. [DOI] [PubMed] [Google Scholar]
  26. Suzuki N., Matsumoto H., Kitada C., Masaki T., Fujino M. A sensitive sandwich-enzyme immunoassay for human endothelin. J Immunol Methods. 1989 Mar 31;118(2):245–250. doi: 10.1016/0022-1759(89)90012-4. [DOI] [PubMed] [Google Scholar]
  27. Vigo-Pelfrey C., Lee D., Keim P., Lieberburg I., Schenk D. B. Characterization of beta-amyloid peptide from human cerebrospinal fluid. J Neurochem. 1993 Nov;61(5):1965–1968. doi: 10.1111/j.1471-4159.1993.tb09841.x. [DOI] [PubMed] [Google Scholar]
  28. Vinters H. V. Cerebral amyloid angiopathy. A critical review. Stroke. 1987 Mar-Apr;18(2):311–324. doi: 10.1161/01.str.18.2.311. [DOI] [PubMed] [Google Scholar]
  29. Vinters H. V., Gilbert J. J. Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke. 1983 Nov-Dec;14(6):924–928. doi: 10.1161/01.str.14.6.924. [DOI] [PubMed] [Google Scholar]
  30. Vinters H. V., Nishimura G. S., Secor D. L., Pardridge W. M. Immunoreactive A4 and gamma-trace peptide colocalization in amyloidotic arteriolar lesions in brains of patients with Alzheimer's disease. Am J Pathol. 1990 Aug;137(2):233–240. [PMC free article] [PubMed] [Google Scholar]
  31. Yamaguchi H., Hirai S., Morimatsu M., Shoji M., Ihara Y. A variety of cerebral amyloid deposits in the brains of the Alzheimer-type dementia demonstrated by beta protein immunostaining. Acta Neuropathol. 1988;76(6):541–549. doi: 10.1007/BF00689591. [DOI] [PubMed] [Google Scholar]

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