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Utility of Cerebrospinal Fluid Transferrin Receptor per Ferritin Ratio in Progressive Supranuclear Palsy
Natsuki Akiyama1, Masato Kanazawa1, Kensaku Kasuga2
1Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
Background:
Progressive supranuclear palsy (PSP) is a major atypical parkinsonism. Because diagnosis based on the cardinal clinical features is often difficult, misdiagnosis with Parkinson's disease (PD) and multiple system atrophy (MSA) is common in PSP patients. Iron metabolism genes are reportedly involved in tau-accumulating neuronal cell death and ferroptosis in PSP, which is more severe than PD and MSA. The validity of transferrin receptor (TfR) expression as a biomarker of ferroptosis was also demonstrated.
Objective:
We investigated whether TfR and the TfR to ferritin ratio in the cerebrospinal fluid (CSF) is a diagnostic biomarker of PSP.
Methods:
This study included 2 independent retrospective CSF cohorts comprising patients, respectively, from Niigata University and a multicenter memory clinic, consisting of patients with PSP, PD, and MSA. All patients were classified as clinically probable or higher based on the Society of Movement Disorders Criteria. TfR and ferritin levels in the CSF were measured using Luminex assay.
Results:
The levels of TfR in patients with PSP were higher than those in patients with PD and MSA in cohort 1 (PSP: N = 16, PD: N = 13, MSA: N = 20). The TfR to ferritin ratio in patients with PSP was significantly higher than that in patients with MSA. Subsequently, we validated these results in cohort 2 (PSP: N = 23, MSA: N = 6). The TfR to ferritin ratio was significantly higher in patients with PSP than in those with MSA.
Conclusions:
The CSF TfR to transferrin ratio was elevated in patients with PSP. These results should be validated in a larger cohort of patients.
