Second-generation radiotracers have improved the use of tau PET in PSP as they have higher affinity for 4R tau isoforms and reduced off-target binding.7718F-PI-2620, a second-generation tau tracer, can detect subcortical tau uptake in PSP and shows significant correlations with NfL, NfL/t-tau and GFAP levels, brain atrophy and cognitive impairment.49 Messerschmidt et al.78 found that using 18F-PI-2620 in addition to MRI measurements of midbrain atrophy improves the diagnostic accuracy of PSP compared with healthy controls. This evidence concerns the gene NEFL and Brain atrophy.