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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins
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ADAM10 Protein
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ADAM17 Protein
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Aged
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Alzheimer Disease / metabolism
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Amyloid Precursor Protein Secretases
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Amyloid beta-Protein Precursor / biosynthesis*
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Amyloid beta-Protein Precursor / genetics
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Animals
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Aspartic Acid Endopeptidases / biosynthesis*
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Aspartic Acid Endopeptidases / genetics
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Autoradiography
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Blotting, Northern
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Brain / embryology
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Brain / metabolism*
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Brain / pathology
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Endopeptidases / biosynthesis*
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Endopeptidases / genetics
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Frontal Lobe / metabolism
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Gene Expression
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Glycoproteins / biosynthesis
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Glycoproteins / genetics
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Humans
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In Situ Hybridization
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Membrane Proteins / biosynthesis*
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Membrane Proteins / genetics
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Metalloendopeptidases / biosynthesis*
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Metalloendopeptidases / genetics
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Metalloendopeptidases / metabolism
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Mice
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Middle Aged
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Neurons / cytology
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Neurons / metabolism
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Parietal Lobe / metabolism
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RNA, Messenger / metabolism
Substances
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Amyloid beta-Protein Precursor
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Glycoproteins
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Membrane Proteins
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RNA, Messenger
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Amyloid Precursor Protein Secretases
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Endopeptidases
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Aspartic Acid Endopeptidases
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BACE2 protein, human
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BACE1 protein, human
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Bace1 protein, mouse
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ADAM Proteins
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Metalloendopeptidases
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ADAM10 Protein
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ADAM10 protein, human
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Adam10 protein, mouse
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ADAM17 Protein
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ADAM17 protein, human
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Adam17 protein, mouse