Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain

J Neurochem. 2000 Nov;75(5):2133-43. doi: 10.1046/j.1471-4159.2000.0752133.x.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins
  • ADAM10 Protein
  • ADAM17 Protein
  • Aged
  • Alzheimer Disease / metabolism
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor / biosynthesis*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Aspartic Acid Endopeptidases / biosynthesis*
  • Aspartic Acid Endopeptidases / genetics
  • Autoradiography
  • Blotting, Northern
  • Brain / embryology
  • Brain / metabolism*
  • Brain / pathology
  • Endopeptidases / biosynthesis*
  • Endopeptidases / genetics
  • Frontal Lobe / metabolism
  • Gene Expression
  • Glycoproteins / biosynthesis
  • Glycoproteins / genetics
  • Humans
  • In Situ Hybridization
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Metalloendopeptidases / biosynthesis*
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism
  • Mice
  • Middle Aged
  • Neurons / cytology
  • Neurons / metabolism
  • Parietal Lobe / metabolism
  • RNA, Messenger / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Glycoproteins
  • Membrane Proteins
  • RNA, Messenger
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE2 protein, human
  • BACE1 protein, human
  • Bace1 protein, mouse
  • ADAM Proteins
  • Metalloendopeptidases
  • ADAM10 Protein
  • ADAM10 protein, human
  • Adam10 protein, mouse
  • ADAM17 Protein
  • ADAM17 protein, human
  • Adam17 protein, mouse