In connection with the development of Alzheimeŕs disease it is important to consider that at least two aspects of metalloproteinase-mediated shedding processes are essential: (i) cleavage of APP by ADAM10 prevents generation of neurotoxic Aβ peptides; (ii) cleavage of full-length RAGE by ADAM10 prevents binding of the RAGE ligand Aβ to cell-bound RAGE [34]. The gene discussed is AGER; the disease is early-onset autosomal dominant Alzheimer disease.