PRNP and Alzheimer disease: Likewise, disastrous synaptic dysfunction and cognitive impairment may be generated by other neurotoxic species equally requiring PrPC as binding receptor; for example, extracellular soluble Aβ oligomers, the 50% of which bind PrPC [27,28,29] (but see [30,31]), and which are AD major initiators [32,33] together with intracellular aggregates of the hyper-phosphorylated tau protein [34]; or α-synuclein oligomers associated with synucleinopathies [35,36].