Prion Protein is Reduced in Aging and in Sporadic but not in Familial Alzheimer's Disease

The cellular form of the prion protein (PrP^C) has been shown to inhibit the production of amyloid-β which is critically involved in the pathogenesis of Alzheimer's disease (AD). We examined the expression of PrP^C by immunoblot analysis in the hippocampus and temporal cortex in sporadic AD, familial AD, and appropriate age-matched controls, and in an aging series (age 20 to 88 years) of brains. PrP^C was reduced by 53% (p = 0.032) in the hippocampus in sporadic AD as compared to the age-matched controls. No such reduction in PrP^C was seen in familial AD. PrP^C was reduced in the hippocampus with aging (r_s = 0.03). The reduction in PrP^C in sporadic but not familial AD suggests that reduced PrP^C expression reflects a primary mechanism of disease and is not merely a secondary consequence of other AD-associated changes. The reduction of PrP^C in the brain with aging suggests that age-related decreases in PrP^C may contribute to the increased incidence of AD in older people.