There are several possible reasons: 1) low affinity of the ligands for 4R tau aggregates/aggregate folds, 2) low density of tau aggregates in PSP tissues, 3) difficulty in distinguishing specific from non-specific binding in basal-ganglia structures, and 4) heterogeneity of tau aggregation and/or tau aggregate folds in 4R tauopathies. This evidence concerns the gene MAPT and tauopathy.