Potential Role of Transferrin and Vascular Cell Adhesion Molecule 1 in Differential Diagnosis Among Patients with Tauopathic Atypical Parkinsonian Syndromes

<b>Background/Objectives:</b> Transferrin is a multi-task protein commonly known for binding iron; however, it is involved in multiple crucial processes, including antimicrobial activity, the growth of different cell types, differentiation, chemotaxis, the cell cycle, and cytoprotection. Vascular cell adhesion molecule 1 (VCAM-1) is a cell surface glycoprotein which participates in inflammation and the trans-endothelial movement of leukocytes. Neither transferrin nor VCAM-1 has been studied in the context of progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS). This study aimed to evaluate the utility of transferrin and VCAM-1 assessment for the in vivo examination of tauopathic atypical Parkinsonian syndromes. <b>Methods</b>: This study included 10 patients with clinically probable PSP-RS, 10 with clinically probable PSP-P, and 8 with probable CBS. Patients' blood and urine were collected and analyzed. Twenty-four serum samples (from twelve males and twelve females) were obtained from age-matched healthy volunteers. Peripheral blood inflammatory ratios, including the neutrophil-to-lymphocyte ratio, the platelet-to-lymphocyte ratio, the neutrophil-to-monocyte ratio, the neutrophil-to-high-density lipoprotein ratio, and the monocyte-to-high-density lipoprotein ratio, were calculated. VCAM-1 and transferrin concentrations were measured in the serum and urine. The urinary biomarker results are not included in the main analysis due to the absence of a control group. <b>Results</b>: The highest concentrations of transferrin in the serum were observed in patients with PSP-P, followed by PSP-RS and CBS. Statistically significant differences were found between PSP-P and healthy controls (<i>p</i> < 0.0001) and PSP-RS and healthy controls (<i>p</i> < 0.0001). The highest levels of serum VCAM-1 were observed in the PSP-P group. Significant differences were found between PSP-P and healthy controls (<i>p</i> < 0.0001), PSP-P and CBS (<i>p</i> < 0.001), and PSP-RS and healthy controls (<i>p</i> < 0.001). Serum VCAM-1 levels were negatively correlated with the NLR in CBS patients (<i>p</i> < 0.03; <i>r</i> = -0.74). Serum transferrin levels were negatively correlated with the NHR in CBS patients (<i>p</i> < 0.04; <i>r</i> = -0.64). ROC curve analyses were conducted to evaluate the diagnostic utility of serum transferrin and VCAM-1 in distinguishing tauopathic APS patients from controls. Transferrin showed excellent diagnostic performance, with an AUC of 0.975 (95% CI: 0.888-0.999; <i>p</i> < 0.0001), a sensitivity of 96.4%, and a specificity of 95.8% at the optimal cut-off (>503.0). VCAM-1 demonstrated good accuracy, with an AUC of 0.839 (95% CI: 0.711-0.926; <i>p</i> < 0.0001), a sensitivity of 75.0%, and a specificity of 91.7% at the optimal cut-off (>463.9). <b>Conclusions:</b> The obtained results indicate the potential role of transferrin and VCAM-1 in the pathogenesis of tauopathic APSs and highlight the need for further exploration in this field.