Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Jan;148(1):259–265.

Amyloid beta protein deposition in normal aging has the same characteristics as that in Alzheimer's disease. Predominance of A beta 42(43) and association of A beta 40 with cored plaques.

H Fukumoto 1, A Asami-Odaka 1, N Suzuki 1, H Shimada 1, Y Ihara 1, T Iwatsubo 1
PMCID: PMC1861616  PMID: 8546214

Abstract

Two distinct species of amyloid beta protein (A beta) with different C-termini, A beta 42(43) and A beta 40, are deposited in senile plaques (SP) of Alzheimer's disease (AD), with the former being far predominant. To investigate whether A beta 42(43) also predominates over A beta 40 in normal aging, we examined by immunocytochemistry the C-termini of A beta in SP in the brains of non-demented aged individuals and compared the results with those in AD. Virtually all SP were A beta 42(43)-positive; of these 12% in non-demented aged individuals and 25% in AD patients (mean of three areas examined) were also A beta 40-positive. In both the AD and non-demented groups, 2/3 of the A beta 40-positive SP were typical cored SP. These results indicate that A beta 42(43) is the predominant species deposited in SP in normal aging, and there is no qualitative difference in terms of the C-terminus of A beta in the parenchymal amyloid deposition between normal aging and AD.

Full text

PDF
259

Images in this article

261Figure 1
on p.261

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arai H., Lee V. M., Otvos L., Jr, Greenberg B. D., Lowery D. E., Sharma S. K., Schmidt M. L., Trojanowski J. Q. Defined neurofilament, tau, and beta-amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2249–2253. doi: 10.1073/pnas.87.6.2249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arriagada P. V., Marzloff K., Hyman B. T. Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease. Neurology. 1992 Sep;42(9):1681–1688. doi: 10.1212/wnl.42.9.1681. [DOI] [PubMed] [Google Scholar]
  3. Barcikowska M., Wisniewski H. M., Bancher C., Grundke-Iqbal I. About the presence of paired helical filaments in dystrophic neurites participating in the plaque formation. Acta Neuropathol. 1989;78(3):225–231. doi: 10.1007/BF00687751. [DOI] [PubMed] [Google Scholar]
  4. Bugiani O., Tagliavini F., Giaccone G., Verga L., el-Hachimi K., Foncin J. F., Frangione B. Diffuse senile plaques: amorphous or fibrous? Am J Pathol. 1995 Mar;146(3):777–779. [PMC free article] [PubMed] [Google Scholar]
  5. Cras P., Kawai M., Lowery D., Gonzalez-DeWhitt P., Greenberg B., Perry G. Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7552–7556. doi: 10.1073/pnas.88.17.7552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crystal H., Dickson D., Fuld P., Masur D., Scott R., Mehler M., Masdeu J., Kawas C., Aronson M., Wolfson L. Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology. 1988 Nov;38(11):1682–1687. doi: 10.1212/wnl.38.11.1682. [DOI] [PubMed] [Google Scholar]
  7. Dickson D. W., Farlo J., Davies P., Crystal H., Fuld P., Yen S. H. Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. Am J Pathol. 1988 Jul;132(1):86–101. [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Hyman B. T., Marzloff K., Arriagada P. V. The lack of accumulation of senile plaques or amyloid burden in Alzheimer's disease suggests a dynamic balance between amyloid deposition and resolution. J Neuropathol Exp Neurol. 1993 Nov;52(6):594–600. doi: 10.1097/00005072-199311000-00006. [DOI] [PubMed] [Google Scholar]
  10. Ihara Y. Massive somatodendritic sprouting of cortical neurons in Alzheimer's disease. Brain Res. 1988 Aug 30;459(1):138–144. doi: 10.1016/0006-8993(88)90293-4. [DOI] [PubMed] [Google Scholar]
  11. Imagawa M., Naruse S., Tsuji S., Fujioka A., Yamaguchi H. Coenzyme Q10, iron, and vitamin B6 in genetically-confirmed Alzheimer's disease. Lancet. 1992 Sep 12;340(8820):671–671. doi: 10.1016/0140-6736(92)92203-r. [DOI] [PubMed] [Google Scholar]
  12. Iwatsubo T., Mann D. M., Odaka A., Suzuki N., Ihara Y. Amyloid beta protein (A beta) deposition: A beta 42(43) precedes A beta 40 in Down syndrome. Ann Neurol. 1995 Mar;37(3):294–299. doi: 10.1002/ana.410370305. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. 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]
  16. Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. doi: 10.1038/325733a0. [DOI] [PubMed] [Google Scholar]
  17. Katzman R., Terry R., DeTeresa R., Brown T., Davies P., Fuld P., Renbing X., Peck A. Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol. 1988 Feb;23(2):138–144. doi: 10.1002/ana.410230206. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Mann D. M. Cerebral amyloidosis, ageing and Alzheimer's disease; a contribution from studies on Down's syndrome. Neurobiol Aging. 1989 Sep-Oct;10(5):397–414. doi: 10.1016/0197-4580(89)90073-0. [DOI] [PubMed] [Google Scholar]
  21. Mann D. M., Iwatsubo T., Fukumoto H., Ihara Y., Odaka A., Suzuki N. Microglial cells and amyloid beta protein (A beta) deposition; association with A beta 40-containing plaques. Acta Neuropathol. 1995;90(5):472–477. doi: 10.1007/BF00294808. [DOI] [PubMed] [Google Scholar]
  22. Mann D. M., Tucker C. M., Yates P. O. The topographic distribution of senile plaques and neurofibrillary tangles in the brains of non-demented persons of different ages. Neuropathol Appl Neurobiol. 1987 Mar-Apr;13(2):123–139. doi: 10.1111/j.1365-2990.1987.tb00176.x. [DOI] [PubMed] [Google Scholar]
  23. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Mullan M., Crawford F., Axelman K., Houlden H., Lilius L., Winblad B., Lannfelt L. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet. 1992 Aug;1(5):345–347. doi: 10.1038/ng0892-345. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Ohnishi T., Nakamura O., Arakaki N., Miyazaki H., Daikuhara Y. Effects of cytokines and growth factors on phosphorylated fetuin biosynthesis by adult rat hepatocytes in primary culture. Biochem Biophys Res Commun. 1994 Apr 15;200(1):598–605. doi: 10.1006/bbrc.1994.1490. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. 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]
  32. 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]
  33. Shin R. W., Ogomori K., Kitamoto T., Tateishi J. Increased tau accumulation in senile plaques as a hallmark in Alzheimer's disease. Am J Pathol. 1989 Jun;134(6):1365–1371. [PMC free article] [PubMed] [Google Scholar]
  34. Suzuki N., Cheung T. T., Cai X. D., Odaka A., Otvos L., Jr, Eckman C., Golde T. E., Younkin S. G. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science. 1994 May 27;264(5163):1336–1340. doi: 10.1126/science.8191290. [DOI] [PubMed] [Google Scholar]
  35. Suzuki N., Iwatsubo T., Odaka A., Ishibashi Y., Kitada C., Ihara Y. High tissue content of soluble beta 1-40 is linked to cerebral amyloid angiopathy. Am J Pathol. 1994 Aug;145(2):452–460. [PMC free article] [PubMed] [Google Scholar]
  36. Terry R. D., Hansen L. A., DeTeresa R., Davies P., Tobias H., Katzman R. Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. J Neuropathol Exp Neurol. 1987 May;46(3):262–268. doi: 10.1097/00005072-198705000-00003. [DOI] [PubMed] [Google Scholar]
  37. Tomlinson B. E., Blessed G., Roth M. Observations on the brains of non-demented old people. J Neurol Sci. 1968 Sep-Oct;7(2):331–356. doi: 10.1016/0022-510x(68)90154-8. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES