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Coordinated Expression of β‐Amyloid Precursor Protein and the Putative β‐Secretase BACE and α‐Secretase ADAM10 in Mouse and Human Brain
Author(s) -
Marcinkiewicz Mieczyslaw,
Seidah Nabil G.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0752133.x
Subject(s) - adam10 , amyloid precursor protein secretase , amyloid precursor protein , in situ hybridization , bace1 as , human brain , alpha secretase , biology , beta (programming language) , alzheimer's disease , neuroscience , microbiology and biotechnology , chemistry , enzyme , biochemistry , metalloproteinase , medicine , messenger rna , gene , disease , disintegrin , computer science , programming language
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 β‐amyloid precursor protein (β‐APP) with those of the putative α‐secretases ADAM10 and ADAM17 and the β‐secretases BACE and BACE2. In situ hybridization performed in mice during prenatal and postnatal development and in adulthood revealed the coexpression of β‐APP, BACE, and ADAM10. The patterns of BACE2 and ADAM17 only partially overlapped with that of β‐APP. β‐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 β‐APP with BACE and ADAM10 in human cortical neurons. Our data provide cytochemical evidence supporting the role of ADAM10 and BACE as authentic α‐ and β‐secretases.

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