Morphology and toxicity of Aβ-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer's disease

Alex E. Roher, Michael O. Chaney, Yu Min Kuo, Scott D. Webster, W. Blaine Stine, Lanny J. Haverkamp, Amina S. Woods, Robert J. Cotter, James M. Tuohy, Grant A. Krafft, Barry S. Bonnell, Mark R. Emmerling

Research output: Contribution to journalArticle

Abstract

In the course of analyzing the chemical composition of Alzheimer's disease neuritic and vascular amyloid, we have purified stable dimeric and trimeric components of Aβ peptides. These peptides (molecular mass 9.0 and 13.5 kDa) were separated by size exclusion chromatography in the presence of 80% formic acid or 5 M guanidine thiocyanate, pH 7.4. The average ratio of monomers, dimers, and trimers was 55:30:15, respectively. Similar structures were produced over time upon incubation of synthetic Aβ-(1-42) at pH 7.4. The stability of these oligomeric forms was also demonstrated by Western blot and mass spectrometry. Atomic force microscopy and electron microscopy rotary shadowing revealed that the monomers polymerized into 8-10-nm filaments, whereas the dimers generated prolate ellipsoids measuring 3-4 nm in diameter. The pathogenic effects of the dimeric Aβ-(1-40/42) were tested in cultures of rat hippocampal neuron glia cells. Only in the presence of microglia did the dimer elicit neuronal killing. It is possible that these potentially pathogenic Aβ(1-40/42) dimers and trimers from Alzheimer's disease amyloid represent the soluble oligomers of Aβ recently described in Alzheimer's disease brains (Kuo, Y.-M., Emmerling, M. R., Vigo-Pelfrey, C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J., and Roher, A. E. (1996) J. Biol. Chem., 271, 4077-4081).

Original languageEnglish (US)
Pages (from-to)20631-20635
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number34
DOIs
StatePublished - 1996

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Amyloid Plaques
Amyloid
Dimers
Blood Vessels
Toxicity
Alzheimer Disease
formic acid
Deposits
Phosmet
Peptides
Atomic Force Microscopy
Monomers
Microglia
Neuroglia
Gel Chromatography
Size exclusion chromatography
Mass Spectrometry
Electron Microscopy
Molecular mass
Western Blotting

ASJC Scopus subject areas

  • Biochemistry

Cite this

Roher, A. E., Chaney, M. O., Kuo, Y. M., Webster, S. D., Stine, W. B., Haverkamp, L. J., ... Emmerling, M. R. (1996). Morphology and toxicity of Aβ-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer's disease. Journal of Biological Chemistry, 271(34), 20631-20635. https://doi.org/10.1074/jbc.271.34.20631

Morphology and toxicity of Aβ-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer's disease. / Roher, Alex E.; Chaney, Michael O.; Kuo, Yu Min; Webster, Scott D.; Stine, W. Blaine; Haverkamp, Lanny J.; Woods, Amina S.; Cotter, Robert J.; Tuohy, James M.; Krafft, Grant A.; Bonnell, Barry S.; Emmerling, Mark R.

In: Journal of Biological Chemistry, Vol. 271, No. 34, 1996, p. 20631-20635.

Research output: Contribution to journalArticle

Roher, AE, Chaney, MO, Kuo, YM, Webster, SD, Stine, WB, Haverkamp, LJ, Woods, AS, Cotter, RJ, Tuohy, JM, Krafft, GA, Bonnell, BS & Emmerling, MR 1996, 'Morphology and toxicity of Aβ-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer's disease', Journal of Biological Chemistry, vol. 271, no. 34, pp. 20631-20635. https://doi.org/10.1074/jbc.271.34.20631
Roher, Alex E. ; Chaney, Michael O. ; Kuo, Yu Min ; Webster, Scott D. ; Stine, W. Blaine ; Haverkamp, Lanny J. ; Woods, Amina S. ; Cotter, Robert J. ; Tuohy, James M. ; Krafft, Grant A. ; Bonnell, Barry S. ; Emmerling, Mark R. / Morphology and toxicity of Aβ-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer's disease. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 34. pp. 20631-20635.
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AU - Stine, W. Blaine

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AU - Woods, Amina S.

AU - Cotter, Robert J.

AU - Tuohy, James M.

AU - Krafft, Grant A.

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