Recently, a knock-in mouse with subtle overexpression of human BACE-1 has been described that seems to reflect certain characteristics of AD in a more physiological way than the multi-transgenic mice: while no monomeric A-beta was detectable, the toxic A-beta hexamer formed from endogenous APP cleavage products was observed and mice displayed cognitive impairment that was intensified by aging [4]. This evidence concerns the gene APP and Alzheimer disease.