In a previous report, we described that the prion acute synaptotoxicity harboured in brains at the terminal stage of M1000 prion disease appeared directly linked to at least modestly PK-resistant PrP species [31]; however, the virtual absence of at least modestly PK-resistant PrP species at 30% and 50% of the TSD (Fig 1A–1C and S1A Fig) regardless of the link between total PrPs and acute synaptotoxicity suggests that synaptotoxic species at earlier time points probably relate to PK-sensitive PrPSc. Here, PRNP is linked to prion disease.