Our results provide evidence that ADAM 10 has alpha-secretase activity and many properties expected for the proteolytic processing of APP. Increases of its expression and activity might be beneficial for the treatment of Alzheimer's disease.;The amyloid precursor protein (APP) undergoes constitutive shedding by a protease activity called a-secretase. This is considered an important mechanism preventing the generation of the Alzheimer’s disease amyloid-b peptide (Ab) [...] We conclude that ADAM10 is the physiologically relevant, constitutive alpha-secretase of APP.