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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 May;144(5):1082–1088.

Development of a monoclonal antibody specific for the COOH-terminal of beta-amyloid 1-42 and its immunohistochemical reactivity in Alzheimer's disease and related disorders.

G M Murphy Jr 1, L S Forno 1, L Higgins 1, J M Scardina 1, L F Eng 1, B Cordell 1
PMCID: PMC1887348  PMID: 8178931

Abstract

The beta-amyloid peptide (beta AP) has been characterized by protein sequencing techniques as a 39-43 amino acid protein with heterogeneous COOH-termini. Controversy exists regarding the predominant form of beta AP in neuritic plaques (NP) and cerebral vasculature of Alzheimer's disease (AD) brain. A monoclonal antibody was developed that selectively recognizes the free COOH-terminal of beta AP 1-42 but not beta AP species with shorter or longer COOH-termini. Brain sections from AD and related disorders were examined using this antibody. In AD samples, the antibody stained diffuse amyloid and NP cores, many intraneuronal and extraneuronal neurofibrillary tangles (NFT), but not cerebrovascular amyloid. Pick and Lewy bodies lacked immunoreactivity. These findings suggest that beta AP 1-42 is present in early and mature amyloid deposits and NFT, but that species of beta AP other than 1-42 comprise human vascular deposits.

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Selected References

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  1. Barrow C. J., Yasuda A., Kenny P. T., Zagorski M. G. Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer's disease. Analysis of circular dichroism spectra. J Mol Biol. 1992 Jun 20;225(4):1075–1093. doi: 10.1016/0022-2836(92)90106-t. [DOI] [PubMed] [Google Scholar]
  2. Forno L. S., DeLanney L. E., Irwin I., Langston J. W. Similarities and differences between MPTP-induced parkinsonsim and Parkinson's disease. Neuropathologic considerations. Adv Neurol. 1993;60:600–608. [PubMed] [Google Scholar]
  3. Halverson K., Fraser P. E., Kirschner D. A., Lansbury P. T., Jr Molecular determinants of amyloid deposition in Alzheimer's disease: conformational studies of synthetic beta-protein fragments. Biochemistry. 1990 Mar 20;29(11):2639–2644. doi: 10.1021/bi00463a003. [DOI] [PubMed] [Google Scholar]
  4. Jarrett J. T., Berger E. P., Lansbury P. T., Jr The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry. 1993 May 11;32(18):4693–4697. doi: 10.1021/bi00069a001. [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. Masters C. L., Multhaup G., Simms G., Pottgiesser J., Martins R. N., Beyreuther K. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 1985 Nov;4(11):2757–2763. doi: 10.1002/j.1460-2075.1985.tb04000.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Miller D. L., Papayannopoulos I. A., Styles J., Bobin S. A., Lin Y. Y., Biemann K., Iqbal K. Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. Arch Biochem Biophys. 1993 Feb 15;301(1):41–52. doi: 10.1006/abbi.1993.1112. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Murphy G. M., Jr, Eng L. F., Ellis W. G., Perry G., Meissner L. C., Tinklenberg J. R. Antigenic profile of plaques and neurofibrillary tangles in the amygdala in Down's syndrome: a comparison with Alzheimer's disease. Brain Res. 1990 Dec 24;537(1-2):102–108. doi: 10.1016/0006-8993(90)90345-c. [DOI] [PubMed] [Google Scholar]
  11. Murphy G. M., Jr, Greenberg B. D., Ellis W. G., Forno L. S., Salamat S. M., Gonzalez-DeWhitt P. A., Lowery D. E., Tinklenberg J. R., Eng L. F. Alzheimer's disease. Beta-amyloid precursor protein expression in the nucleus basalis of Meynert. Am J Pathol. 1992 Aug;141(2):357–361. [PMC free article] [PubMed] [Google Scholar]
  12. Murphy G. M., Jr, Murphy E., Greenberg B. D., Cordell B., Eng L. F., Ellis W. G., Forno L. S., Salamat S. M., Gonzalez-DeWhitt P. A., Lowery D. E. Alzheimer's disease: beta-amyloid precursor protein expression in plaques varies among cytoarchitectonic areas of the medial temporal lobe. Neurosci Lett. 1991 Sep 30;131(1):100–104. doi: 10.1016/0304-3940(91)90346-u. [DOI] [PubMed] [Google Scholar]
  13. Perry G., Cras P., Siedlak S. L., Tabaton M., Kawai M. Beta protein immunoreactivity is found in the majority of neurofibrillary tangles of Alzheimer's disease. Am J Pathol. 1992 Feb;140(2):283–290. [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Prelli F., Levy E., van Duinen S. G., Bots G. T., Luyendijk W., Frangione B. Expression of a normal and variant Alzheimer's beta-protein gene in amyloid of hereditary cerebral hemorrhage, Dutch type: DNA and protein diagnostic assays. Biochem Biophys Res Commun. 1990 Jul 16;170(1):301–307. doi: 10.1016/0006-291x(90)91274-v. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Taggart R. T., Samloff I. M. Stable antibody-producing murine hybridomas. Science. 1983 Mar 11;219(4589):1228–1230. doi: 10.1126/science.6402815. [DOI] [PubMed] [Google Scholar]

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