Processing of the beta-amyloid precursor protein in ex vivo human brain cells.
We studied distribution and processing of the Alzheimer's beta-amyloid precursor protein (betaAPP) in immediately ex vivo human brain cells obtained during neurosurgical procedures. Immunoblotting and flow cytometry studies revealed that brain cells supported betaAPP as a transmembrane holoprotein. Brain cells in short-term suspension culture were competent to process betaAPP into Abeta as shown by [35S]methionine pulse-chase studies. Brain cell Abeta was immunoprecipitated as SDS-stable dimers and higher-order multimers. Cleavage of cell surface betaAPP with trypsin prior to metabolic labeling reduced cellular Abeta by approximately 50%. We conclude that plasmalemmal betaAPP in human brain cells is a source of cellular Abeta, presumably via endosomal-lysosomal processing.
Jung
S S
SS
Department of Microbiology and Immunology, Montréal Neurological Institute, McGill University, PQ, Canada.
Cashman
N R
NR
D000293:Adolescent; D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor