Up to recent years, commonalities between the amyloid precursor protein (APP) and the cellular prion protein PrPc were considered to mainly reside in their capacity to give rise to aggregation-prone proteins, amyloid beta (Aβ) and PrPSc (standing for scrapie isoform of the prion protein), both involved in neurodegenerative disorders, Alzheimer’s disease (AD) and transmissible spongiform encephalopathies (TSEs), respectively (Haass and Selkoe, 2007; Aguzzi and Calella, 2009). Here, APP is linked to human prion disease.