One or more β-amyloid(s)? New insights into the prion-like nature of Alzheimer's disease

Abstract

Misfolding and aggregation of proteins play a central role in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's and Lewy Body diseases, Frontotemporal Lobar Degeneration and prion diseases. Increasing evidence supports the view that Aβ and tau, which are the two main molecular players in AD, share with the prion protein several "prion-like" features that can be relevant for disease pathogenesis. These features essentially include structural/conformational/biochemical variations, resistance to degradation by endogenous proteases, seeding ability, attitude to form neurotoxic assemblies, spreading and propagation of toxic aggregates, transmissibility of tau- and Aβ-related pathology to animal models. Following this view, part of the recent scientific literature has generated a new reading frame for AD pathophysiology, based on the application of the prion paradigm to the amyloid cascade hypothesis in an attempt to definitely explain the key events causing the disease and inducing its occurrence under different clinical phenotypes.

Keywords: Alzheimer's disease; Amyloid; Aβ; Misfolding; Oligomers; Phenotypes; PrP; Prion; Prion-like; Tau.