ADAM19 is tightly associated with constitutive Alzheimer’s disease APP α-secretase in A172 cells

To elucidate whether new proteases are involved in the processing of amyloid precursor protein (APP), we examined catalytically active ADAM12 and ADAM19 as candidates α-secretases. The overexpression of ADAM19 in HEK293 cells resulted in an increase in sAPPα. Therefore, we suggest that ADAM19 has a constitutive α-secretase activity. We examined regulated α-secretase activity by adding phorbol 12-myristate 13-acetate (PMA), but no regulated activity was found. To verify that endogenous ADAM19 has an APP α-secretase activity, we examined whether the constitutive level of α-secretase activity was reduced by RNA interference with ADAM19 in A172 cells. The amount of secreted sAPPα decreased by about 21% following RNAi. These results suggest that ADAM19 has a constitutive α-secretase activity for APP.