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Science 7 February 1992:
Vol. 255. no. 5045, pp. 726 - 728
DOI: 10.1126/science.1738846
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Articles

Science, Vol 255, Issue 5045, 726-728
Copyright © 1992 by American Association for the Advancement of Science

articles

Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor

S Estus, TE Golde, T Kunishita, D Blades, D Lowery, M Eisen, M Usiak, XM Qu, T Tabira, BD Greenberg, and al. et

Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106.

The 39- to 43-amino acid amyloid beta protein (beta AP), which is deposited as amyloid in Alzheimer's disease, is encoded as an internal peptide that begins 99 residues from the carboxyl terminus of a 695- to 770-amino acid glycoprotein referred to as the amyloid beta protein precursor (beta APP). To clarify the processing that produces amyloid, carboxyl-terminal derivatives of the beta APP were analyzed. This analysis showed that the beta APP is normally processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives. The two largest derivatives in human brain have the entire beta AP at or near their amino terminus and are likely to be intermediates in the pathway leading to amyloid deposition.


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Soluble beta-amyloid induction of Alzheimer's phenotype for human fibroblast K+ channels.
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Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors.
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Production of the Alzheimer amyloid beta protein by normal proteolytic processing.
M Shoji, T. Golde, J Ghiso, T. Cheung, S Estus, L. Shaffer, X. Cai, D. McKay, R Tintner, B Frangione, et al. (1992)
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Alzheimer's disease: a cell biological perspective.
K. Kosik (1992)
Science 256, 780-783
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Alzheimer's disease: the amyloid cascade hypothesis.
J. Hardy and G. Higgins (1992)
Science 256, 184-185
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Processing of the amyloid protein precursor to potentially amyloidogenic derivatives.
T. Golde, S Estus, L. Younkin, D. Selkoe, and S. Younkin (1992)
Science 255, 728-730
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A Novel gamma -Secretase Assay Based on Detection of the Putative C-terminal Fragment-gamma of Amyloid beta Protein Precursor.
I. Pinnix, U. Musunuru, H. Tun, A. Sridharan, T. Golde, C. Eckman, C. Ziani-Cherif, L. Onstead, and K. Sambamurti (2001)
J. Biol. Chem. 276, 481-487
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