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

Agnieszka Kulczyńska-Przybik,Barbara Mroczko,Maciej Dulewicz,Alina Kułakowska,Renata Borawska,Agnieszka Słowik,Jan Kochanowicz

doi:10.3390/jcm10225281

Agnieszka Kulczyńska-Przybik, Barbara Mroczko + Show 5 more

Open Access

https://doi.org/10.3390/jcm10225281

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Abstract

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.

Highlights

Introduction iationsNeurodegenerative diseases (NDs) are the most common cause of cognitive impairment and a growing cause of morbidity and mortality worldwide, in older adults
The study population consisted of 98 subjects with neurological disorders (64 women and 34 men, median of age 66 years), who were divided into four subgroups: patients with Alzheimer’s disease (AD) (n = 20), patients with Parkinson disease (PD) (n = 19), patients with Multiple sclerosis (MS) (n = 38), and non-demented subjects as a control group (n = 21) (Table 1)
Our research showed a significant difference in the concentrations of the tested protein between AD and PD as well as AD and MS, which indicates the possibility of using it as a biomarker in the differential diagnosis of cognitive disorders

Summary

Introduction

Neurodegenerative diseases (NDs) are the most common cause of cognitive impairment and a growing cause of morbidity and mortality worldwide, in older adults. NDs are still incurable, difficult to detect them at earlier stages due to the long asymptomatic incubation period, and hard to differentiate at later stages due to the similarities of different NDs or their atypical forms [1,2]. It is important to discriminate and diagnose these disorders accurately [3]. Biomarkers that might improve the diagnosis of these diseases are urgently sought. There are no universally accepted biomarkers with confirmed reliability as a measure of disease burden in NDs, except CSF biomarkers for Alzheimer’s disease, which is a significant problem in clinical practice [3]. Many investigations of potential biomarkers have been carried out in CSF of patients with ND.

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