The Prion-Like Properties of Amyloid-ß Assemblies: Implications for Alzheimer's Disease.

ABSTRACT

Since the discovery that prion diseases can be transmitted to experimental animals by inoculation with afflicted brain matter, researchers have speculated that the brains of patients suffering from other neurodegenerative diseases might also harbor causative agents with transmissible properties. Foremost among these disorders is Alzheimer's disease (AD), the most common cause of dementia in the elderly. A growing body of research supports the concept that the pathogenesis of AD is initiated and sustained by the endogenous, seeded misfolding and aggregation of the protein fragment amyloid-ß (Aß). At the molecular level, this mechanism of nucleated protein self-assembly is virtually identical to that of prions consisting of the prion protein (PrP). The formation, propagation, and spread of Aß seeds within the brain can thus be considered a fundamental feature of AD pathogenesis.