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Keywords:

  • mRNA colocalization;
  • Mouse ontogeny;
  • ADAM17;
  • BACE2;
  • Diffuse amyloid plaques;
  • Presenile Alzheimer's subjects;
  • Etiology of Alzheimer's disease

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 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.