In this study we have demonstrated a significant inverse correlation between PrPC and BACE1 activity in cortex from patients with sporadic AD (in whom PrPC level is lower and BACE1 activity higher than in age-matched controls) but not in Down's syndrome, despite the accumulation of Aβ and the presence of other AD-type pathological abnormalities in the latter. Here, PRNP is linked to Down syndrome.