title: Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain.
abstract: To define the enzymes involved in the etiology of Alzheimer's disease, we compared in mouse and human brain the mRNA levels and cellular localization of the ubiquitous beta-amyloid precursor protein (beta-APP) with those of the putative alpha-secretases ADAM10 and ADAM17 and the beta-secretases BACE and BACE2. In situ hybridization performed in mice during prenatal and postnatal development and in adulthood revealed the coexpression of beta-APP, BACE, and ADAM10. The patterns of BACE2 and ADAM17 only partially overlapped with that of beta-APP. beta-APP, BACE, and ADAM10 mRNAs have also been detected by northern blot in human brain cortex of normal subjects and in Alzheimer's disease subjects. In situ hybridization performed using combined biotin- and radiolabeled riboprobes provided evidence for the coexpression of beta-APP with BACE and ADAM10 in human cortical neurons. Our data provide cytochemical evidence supporting the role of ADAM10 and BACE as authentic alpha- and beta-secretases.
authors.affiliation: Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. Marcinm@ircm.qc.ca
authors.forename: M
authors.initials: M
authors.lastname: Marcinkiewicz
authors.forename: N G
authors.initials: NG
authors.lastname: Seidah
mesh_terms: D051722:ADAM Proteins; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D001345:Autoradiography; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D010450:Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D005625:Frontal Lobe / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010296:Parietal Lobe / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D006023:Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; C491234:Adam10 protein, mouse; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse