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. 1996 Jun;148(6):1749–1756.

Selective binding of soluble Abeta1-40 and Abeta1-42 to a subset of senile plaques.

R Prior 1, D D'Urso 1, R Frank 1, I Prikulis 1, S Cleven 1, R Ihl 1, G Pavlakovic 1
PMCID: PMC1861649  PMID: 8669461

Abstract

Alzheimer's disease is characterized by the progressive accumulation of amyloid-beta protein (Abeta) in senile plaques and cerebral amyloid angiopathy. It is not known whether the plaque growth is a continuous and homogeneous process or whether some plaques have a more rapid evolution. As plaques grow by the deposition of Abeta, we used an in situ binding technique to analyze the deposition of fluorescein-conjugated and biotinylated Abeta1 40 and Abeta1-42 in cryosections of brains from Alzheimer's disease patients. Only a subset of senile plaques but all cerebrovascular Abeta deposits were labeled by both Abeta1-40 and Abeta1-42. Striking differences in binding were observed among adjacent plaques. Quantitative analysis showed that on average 60% of all plaques were labeled with Abeta1-42 and 31% of all plaques were labeled with Abeta1-40 (n=7; P<0.001). Confocal laser scanning microscopy of double-labeled sections revealed that the newly deposited Abeta was only partially co-localized to pre-existing Abeta and apolipoprotein E and was not co-localized to heparan sulfate proteoglycan. Abeta binding was preserved after glycolytic pretreatment with periodic acid. Our results suggest that at a given time point only a subset of active senile plaques accumulate A(beta) and that plaque growth may be conditioned by the presence of other distinct plaque components different from Abeta, apolipoprotein E or heparan sulfate proteoglycan.

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Selected References

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

  1. Burdick D., Soreghan B., Kwon M., Kosmoski J., Knauer M., Henschen A., Yates J., Cotman C., Glabe C. Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs. J Biol Chem. 1992 Jan 5;267(1):546–554. [PubMed] [Google Scholar]
  2. Buée L., Ding W., Delacourte A., Fillit H. Binding of secreted human neuroblastoma proteoglycans to the Alzheimer's amyloid A4 peptide. Brain Res. 1993 Jan 22;601(1-2):154–163. doi: 10.1016/0006-8993(93)91706-x. [DOI] [PubMed] [Google Scholar]
  3. Castano E. M., Prelli F., Wisniewski T., Golabek A., Kumar R. A., Soto C., Frangione B. Fibrillogenesis in Alzheimer's disease of amyloid beta peptides and apolipoprotein E. Biochem J. 1995 Mar 1;306(Pt 2):599–604. doi: 10.1042/bj3060599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gravina S. A., Ho L., Eckman C. B., Long K. E., Otvos L., Jr, Younkin L. H., Suzuki N., Younkin S. G. Amyloid beta protein (A beta) in Alzheimer's disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43). J Biol Chem. 1995 Mar 31;270(13):7013–7016. doi: 10.1074/jbc.270.13.7013. [DOI] [PubMed] [Google Scholar]
  5. Gupta-Bansal R., Frederickson R. C., Brunden K. R. Proteoglycan-mediated inhibition of A beta proteolysis. A potential cause of senile plaque accumulation. J Biol Chem. 1995 Aug 4;270(31):18666–18671. doi: 10.1074/jbc.270.31.18666. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Iwatsubo T., Odaka A., Suzuki N., Mizusawa H., Nukina N., Ihara Y. Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron. 1994 Jul;13(1):45–53. doi: 10.1016/0896-6273(94)90458-8. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. LaDu M. J., Falduto M. T., Manelli A. M., Reardon C. A., Getz G. S., Frail D. E. Isoform-specific binding of apolipoprotein E to beta-amyloid. J Biol Chem. 1994 Sep 23;269(38):23403–23406. [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. Maury C. P. Molecular pathogenesis of beta-amyloidosis in Alzheimer's disease and other cerebral amyloidoses. Lab Invest. 1995 Jan;72(1):4–16. [PubMed] [Google Scholar]
  13. Näslund J., Thyberg J., Tjernberg L. O., Wernstedt C., Karlström A. R., Bogdanovic N., Gandy S. E., Lannfelt L., Terenius L., Nordstedt C. Characterization of stable complexes involving apolipoprotein E and the amyloid beta peptide in Alzheimer's disease brain. Neuron. 1995 Jul;15(1):219–228. doi: 10.1016/0896-6273(95)90079-9. [DOI] [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. Prior R., D'Urso D., Frank R., Prikulis I., Pavlakovic G. Experimental deposition of Alzheimer amyloid beta-protein in canine leptomeningeal vessels. Neuroreport. 1995 Sep 11;6(13):1747–1751. doi: 10.1097/00001756-199509000-00010. [DOI] [PubMed] [Google Scholar]
  16. Richey P. L., Siedlak S. L., Smith M. A., Perry G. Apolipoprotein E interaction with the neurofibrillary tangles and senile plaques in Alzheimer disease: implications for disease pathogenesis. Biochem Biophys Res Commun. 1995 Mar 17;208(2):657–663. doi: 10.1006/bbrc.1995.1389. [DOI] [PubMed] [Google Scholar]
  17. 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]
  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. Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease. Annu Rev Cell Biol. 1994;10:373–403. doi: 10.1146/annurev.cb.10.110194.002105. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Snow A. D., Mar H., Nochlin D., Kimata K., Kato M., Suzuki S., Hassell J., Wight T. N. The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease. Am J Pathol. 1988 Dec;133(3):456–463. [PMC free article] [PubMed] [Google Scholar]
  23. Snow A. D., Sekiguchi R., Nochlin D., Fraser P., Kimata K., Mizutani A., Arai M., Schreier W. A., Morgan D. G. An important role of heparan sulfate proteoglycan (Perlecan) in a model system for the deposition and persistence of fibrillar A beta-amyloid in rat brain. Neuron. 1994 Jan;12(1):219–234. doi: 10.1016/0896-6273(94)90165-1. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Strittmatter W. J., Weisgraber K. H., Huang D. Y., Dong L. M., Salvesen G. S., Pericak-Vance M., Schmechel D., Saunders A. M., Goldgaber D., Roses A. D. Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8098–8102. doi: 10.1073/pnas.90.17.8098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Su J. H., Cummings B. J., Cotman C. W. Localization of heparan sulfate glycosaminoglycan and proteoglycan core protein in aged brain and Alzheimer's disease. Neuroscience. 1992 Dec;51(4):801–813. doi: 10.1016/0306-4522(92)90521-3. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. 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]

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