Binding between Prion Protein and Aβ Oligomers Contributes to the Pathogenesis of Alzheimer's Disease.

A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases, such as prion diseases and Alzheimer's disease (AD). Like prion diseases, AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential. Although it remains elusive how protein aggregation leads to AD, it is becoming clear that cellular prion protein (PrP) plays an important role in AD pathogenesis. Here, we briefly reviewed AD pathogenesis and focused on recent progresses how PrP contributed to AD development. In addition, we proposed a potential mechanism to explain why infectious agents, such as viruses, conduce AD pathogenesis. Microbe infections cause Aβ deposition and upregulation of PrP, which lead to high affinity binding between Aβ oligomers and PrP. The interaction between PrP and Aβ oligomers in turn activates the Fyn signaling cascade, resulting in neuron death in the central nervous system (CNS). Thus, silencing PrP expression may turn out be an effective treatment for PrP dependent AD.