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

To define the enzymes involved in the etiology of Alzheimer's disease, we c ompared in mouse and human brain the mRNA levels and cellular localization of the ubiquitous beta-amyloid precursor protein (beta-APP) with those of t he putative alpha-secretases ADAM10 and ADAM17 and the beta-secretases BACE and BACE2. In situ hybridization performed in mice during prenatal and pos tnatal development and in adulthood revealed the coexpression of beta-APP, BACE, and ADAM10. The patterns of BACE2 and ADAM17 only partially overlappe d with that of beta-APP. beta-APP, BACE, and ADAM10 mRNAs have also been de tected by northern blot in human brain cortex of normal subjects and in Alz heimer's disease subjects. In situ hybridization performed using combined b iotin- and radiolabeled riboprobes provided evidence for the coexpression o f 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.