Akiyama Natsuki, Kanazawa Masato, Kasuga Kensaku, Hatakeyama Masahiro, Ikeuchi Takeshi, Onodera Osamu
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
Mov Disord Clin Pract. 2025 Apr;12(4):446-452. doi: 10.1002/mdc3.14313. Epub 2024 Dec 17.
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.
We investigated whether TfR and the TfR to ferritin ratio in the cerebrospinal fluid (CSF) is a diagnostic biomarker of PSP.
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.
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.
The CSF TfR to transferrin ratio was elevated in patients with PSP. These results should be validated in a larger cohort of patients.
进行性核上性麻痹（PSP）是一种主要的非典型帕金森综合征。由于基于主要临床特征进行诊断往往困难，PSP患者中误诊为帕金森病（PD）和多系统萎缩（MSA）的情况很常见。据报道，铁代谢基因参与PSP中tau蛋白聚集的神经元细胞死亡和铁死亡，PSP中的这种情况比PD和MSA更严重。转铁蛋白受体（TfR）表达作为铁死亡生物标志物的有效性也得到了证实。
我们研究了脑脊液（CSF）中转铁蛋白受体（TfR）及其与铁蛋白的比值是否为PSP的诊断生物标志物。
本研究纳入了2个独立的回顾性脑脊液队列，分别来自新潟大学和一个多中心记忆诊所，包括PSP、PD和MSA患者。所有患者均根据运动障碍协会标准被分类为临床可能或更高。使用Luminex检测法测量脑脊液中的TfR和铁蛋白水平。
在队列1中，PSP患者（n = 16）的TfR水平高于PD患者（n = 13）和MSA患者（n = 20）。PSP患者的TfR与铁蛋白比值显著高于MSA患者。随后，我们在队列2中（PSP：n = 23，MSA：n = 6）验证了这些结果。PSP患者的TfR与铁蛋白比值显著高于MSA患者。
PSP患者脑脊液中TfR与转铁蛋白的比值升高。这些结果应在更大规模的患者队列中进行验证。
