Alzheimer's disease and Creutzfeldt-Jakob disease: overlap of pathogenic mechanisms.

This article compares beta-amyloid precursor protein (beta-APP) disorders exemplified by Alzheimer's disease (AD), with prion protein (PrP) disorders, exemplified by Creutzfeldt-Jakob disease (CJD) in humans and scrapie in animals. Although there are obvious differences in the etiology and pathogenesis of both sets of disorders, a remarkable number of similarities exist. Both sets of disorders are characterized clinically by age-related sporadic and familial diseases. In both, an abnormal form of a neuronal membrane protein appears to play a key role in the pathogenesis: beta-A4 peptide in AD and PrPCJD in CJD. Both beta-A4 and PrPCJD are amyloidogenic. Neuritic plaques characteristic of AD were once thought to be exclusively associated with beta-A4 amyloid; however, some pedigrees with familial prion disease produced neuritic plaques with PrP amyloid cores. Finally, beta-APP accumulation in skeletal muscle has been implicated in the age-related muscle disorder, inclusion body myositis. A similar myopathy has recently been discovered in transgenic mice expressing high levels of normal PrP. These similarities suggest that what is learned about one set of disorders may be applicable to the other.