PrPC inhibited the action of BACE1 towards wild type human APP in cellular models and the levels of endogenous murine Aβ were significantly increased in the brain of PrPC null mice [15], and we proposed that a normal function of PrPC may be to protect against AD [16], i.e. that BACE1 activity is negatively modulated by PrPC, which thereby influences Aβ load and the onset and severity of AD. This evidence concerns the gene PRNP and Alzheimer disease.