PrPC can misfold to form the toxic scrapie (PrPSc) conformation causative for infectious prion diseases.1−4 PrPC can also interact with other aggregation-prone proteins,5−8 such as amyloid-β (Aβ),8 andits high affinity for the Aβ oligomer (Aβo) has been knownto trigger Alzheimer’s disease (AD) pathophysiology.9,10 However, while structural descriptions of the PrPC andPrPSc forms have been reported, it remains unclear howPrP transitions from one state to another and how its toxicity isachieved.11−14. Here, PRNP is linked to early-onset autosomal dominant Alzheimer disease.