Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues.
Progressive cerebral deposition of extracellular filaments composed of the beta-amyloid protein (beta AP) is a constant feature of Alzheimer disease (AD). Since the gene on chromosome 21 encoding the beta AP precursor (beta APP) is not known to be altered in AD, transcriptional or posttranslational changes may underlie accelerated beta AP deposition. Using two antibodies to the predicted carboxyl terminus of beta APP, we have identified the native beta APP in brain and nonneural human tissues as a 110- to 135-kDa protein complex that is insoluble in buffer and found in various membrane-rich subcellular fractions. These proteins are relatively uniformly distributed in adult brain, abundant in fetal brain, and detected in nonneural tissues that contain beta APP mRNA. Similarly sized proteins occur in rat, cow, and monkey brain and in cultured human HL-60 and HeLa cells; the precise patterns in the 110- to 135-kDa range are heterogeneous among various tissues and cell lines. Confirmation that the immunodetected tissue proteins are forms of beta APP was obtained when mammalian cells transfected with a full-length beta APP cDNA showed selectively augmented expression of 110- to 135-kDa proteins and specific immunocytochemical staining. Unexpectedly, the antibodies to the carboxyl terminus of beta APP labeled amyloid-containing senile plaques in AD brain. We conclude that the highly conserved beta APP molecule occurs in mammalian tissues as a heterogeneous group of membrane-associated proteins of approximately 120 kDa. Detection of the nonamyloidogenic carboxyl terminus within plaques suggests that proteolytic processing of the beta APP into insoluble filaments occurs locally in cortical regions that develop beta-amyloid deposits with age.
D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000032:analysis* / Q000235:genetics; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002891:Chromosomes, Human, Pair 21; D004247:DNA / Q000032:analysis; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis*; D008970:Molecular Weight; D011498:Protein Precursors / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D004247:DNA