Direct comparison between 18F-Flortaucipir tau PET and quantitative susceptibility mapping in progressive supranuclear palsy

The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases

“…Iron dysregulation in 15 PSP-P and 14 PSP-RS patients was found to be comparable in another study as well [92]. Supporting the possible relationship of the observed subtype-specific iron differences to varying tau pathologies, 19 PSP-RS patients' brains showed a strong correlation with iron and tau levels in the cerebellar dentate, and 10 PSP-P patients' brains showed a strong correlation with iron and tau levels in the putamen, subthalamic nucleus, and the red nucleus [87]. Such observations suggest that cortical alterations in the iron levels may be present at the early stages of cortical variants [86].…”

“…A recent study by Tanaka et al [89] demonstrates the PSP-specific involvement of tau deposition in the cranial and spinal nerves, including the oculomotor nerve, supporting a tight association between iron and tau in PSP. Accordingly, the correlations between susceptibility and flortaucipir uptake were shown to be significantly positive in the putamen, pallidum, subthalamic nucleus, RN, and the dentate nucleus of PSP patients, and it was suggested that susceptibility measures may mediate or explain the levels of flortaucipir uptake [87]. Furthermore, regional iron accumulation has been shown to correlate with atrophy as well as clinical severity in 13 and 51 PSP-affected brains, respectively [83,90,91], further supporting its involvement in disease pathology.…”

“…However, in vivo, PSP patients were devoid of any increase in cortical iron levels observed via MRI in 12 and 40 PSP patients [27,86]. Nevertheless, Satoh et al [87] reported positive associations between susceptibility and flortaucipir uptake in the bilateral frontal white matter and the right fusiform region in 50 PSP patients, suggesting there may be pathology-associated changes in iron homeostasis at lower concentrations in PSP cortical regions. Interestingly, iron accumulation has also been observed along the oculomotor nerve of six PSP brains, which has not been observed in aged controls [88].…”

“…Furthermore, regional iron accumulation has been shown to correlate with atrophy as well as clinical severity in 13 and 51 PSP-affected brains, respectively [83,90,91], further supporting its involvement in disease pathology. Accordingly, iron deposition patterns have recently been compared in different PSP clinical subtypes for a possible stratification [86,87,92]. PSP-Parkinsonism (PSP-P; n = 9) accounted for the greatest number of regions with significantly high iron levels compared to controls (pallidum, subthalamic nucleus, SN, RN, cerebellar dentate), followed by PSP-Richardson syndrome (PSP-RS; n = 20) (pallidum, SN, RN, cerebellar dentate) and PSP-postural instability (PSP-PI; n = 4) (pallidum, SN), whereas PSP-progressive gait freezing (PSP-PGF; n = 7) did not exhibit any differences in all regions.…”