Journal article

Processing of the Alzheimer's disease amyloid precursor protein in Pichia pastoris: Immunodetection of alpha-, beta-, and gamma-secretase products

D Le Brocque, A Henry, R Cappai, QX Li, JE Tanner, D Galatis, C Gray, S Holmes, JR Underwood, K Beyreuther, CL Masters, G Evin



betaA4 (Abeta) amyloid peptide, a major component of Alzheimer's disease (AD) plaques, is a proteolytic product of the amyloid precursor protein (APP). Endoproteases, termed beta- and gamma-secretase, release respectively the N- and C-termini of the peptide. APP default secretion involves cleavage within the betaA4 domain by alpha-secretase. To study the conservation of APP processing in lower eukaryotes, the yeast Pichia pastoris was transfected with human APP695 cDNA. In addition to the full-length integral transmembrane protein found in the cell lysate, soluble/secreted APP (sAPP) was detected in the culture medium. Most sAPP comprised the N-terminal moiety of betaA4 and corresponds to sA..

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