Together with the observation that PrPC was decreased in the brains from sporadic AD individuals and that the amount of PrPC inversely correlated with BACE1 activity, soluble and insoluble Aβ and Braak stage in the human brain [10,11], led us to propose that PrPC may function to protect against AD and that loss of PrPC would lead to the earlier onset of AD [12,13]. This evidence concerns the gene BACE1 and Alzheimer disease.