β-Amyloid Prions and the Pathobiology of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease in humans and will pose a considerable challenge to healthcare systems in the coming years. Aggregation of the β-amyloid (Aβ) peptide within the brain is thought to be an initiating event in AD pathogenesis. Many recent studies in transgenic mice have provided evidence that Aβ aggregates become self-propagating during disease, leading to a cascade of protein aggregation in the brain, which may underlie the progressive nature of AD. The ability to self-propagate and the existence of distinct "strains" reveals that Aβ aggregates exhibit many properties indistinguishable from those of prions composed of PrP^Sc proteins. Here, we review the evidence that Aβ can become a prion during disease and discuss how Aβ prions may be important for understanding the pathobiology of AD.