The Clinical Significance of Cerebrospinal Fluid Reticulon 4 (RTN4) Levels in the Differential Diagnosis of Neurodegenerative Diseases

Neurodegenerative diseases (NDs) belong to the top global causes of mortality. Diagnostic approaches to improve early diagnosis and differentiation of these diseases are constantly being sought. Therefore, we aimed to assess the cerebrospinal fluid (CSF) concentrations of Reticulon 4 (RTN4) in patients with neurodegenerative diseases and evaluate the potential clinical usefulness of this protein. RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. According to our best knowledge, this is the first investigation providing the data concerning the dynamic of CSF RTN4 protein levels in patients with different NDs. Methods: Overall, 77 newly diagnosed patients with neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), as well as 21 controls, were enrolled in the study. The CSF concentrations of tested proteins were assessed using immunological assays. Results: We revealed significantly higher CSF RTN4A levels in patients with AD, PD, and MS in comparison to the controls. Moreover, the comparative analysis of RTN4 concentration between different neurodegenerative diseases revealed the highest concentration of RTN4A in AD patients and a statistically significant difference between AD vs. PD, and AD vs. MS groups. The increased CSF level of the protein correlated with Tau, and pTau181 proteins in AD as well as in PD patients. Conclusions: Our study presents a previously not identified clinical utility of RTN4 in the differential diagnosis of neurodegenerative diseases.

Automated summary

The study evaluated the concentrations of the RTN4 protein in the cerebrospinal fluid of patients with neurodegenerative diseases, finding significantly higher levels in AD, PD, and MS patients compared to controls. Additionally, the highest concentration of RTN4A was found in AD patients, with a significant difference between AD vs. PD and AD vs. MS groups.