PRNP and tauopathy: Interestingly, it has been shown that cofactors can cause strain adaptation in the prion protein, with the incorporation of a different cofactor leading to changes in strain conformation and infectivity.69 Furthermore, poly(ADP-ribose) has been shown to act as a cofactor for α-synuclein aggregation, leading to the formation of a highly toxic α-synuclein strain.70 The aggregated tau conformers found in different tauopathies could each have a unique combination of cofactors depending on their brain region and environment, which may serve as a unique biomarker and therapeutic target.