Evidence that beta-amyloid protein in Alzheimer's disease is not derived by normal processing.
The beta-amyloid protein (beta/A4), derived from a larger amyloid precursor protein (APP), is the principal component of senile plaques in Alzheimer's disease. APP is an integral membrane glycoprotein and is secreted as a carboxyl-terminal truncated molecule. APP cleavage, which is a membrane-associated event, occurred at a site located within the beta/A4 region. This suggests that an intact amyloidogenic beta/A4 fragment is not generated during normal APP catabolism. Therefore, an early event in amyloid formation may involve altered APP processing that results in the release and subsequent deposition of intact beta/A4.
Sisodia
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Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2181.
Koo
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Beyreuther
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Unterbeck
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Price
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D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002462:Cell Membrane; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004274:DNA, Recombinant; D006031:Glycosylation; D006207:Half-Life; D006801:Humans; D015151:Immunoblotting; D008970:Molecular Weight; D010957:Plasmids; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013373:Substance P / Q000235:genetics; D014162:Transfection
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004274:DNA, Recombinant; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D013373:Substance P