Kulczyńska-Przybik Agnieszka, Dulewicz Maciej, Słowik Agnieszka, Borawska Renata, Kułakowska Alina, Kochanowicz Jan, Mroczko Barbara
Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland.
Department of Neurology, Jagiellonian University, 30-688 Kraków, Poland.
J Clin Med. 2021 Nov 13;10(22):5281. doi: 10.3390/jcm10225281.
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.
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.
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.
Our study presents a previously not identified clinical utility of RTN4 in the differential diagnosis of neurodegenerative diseases.
神经退行性疾病（NDs）是全球主要的死亡原因之一。人们一直在不断寻求改善这些疾病早期诊断和鉴别诊断的方法。因此，我们旨在评估神经退行性疾病患者脑脊液（CSF）中网状蛋白4（RTN4）的浓度，并评估这种蛋白质潜在的临床应用价值。RTNs是跨膜蛋白，介导中枢神经系统损伤或疾病后的神经解剖可塑性和功能恢复。据我们所知，这是首次提供不同NDs患者脑脊液RTN4蛋白水平动态数据的研究。
本研究共纳入77例新诊断的神经退行性疾病患者，包括阿尔茨海默病（AD）、帕金森病（PD）和多发性硬化症（MS），以及21名对照者。使用免疫测定法评估受试蛋白的脑脊液浓度。
我们发现，与对照组相比，AD、PD和MS患者的脑脊液RTN4A水平显著更高。此外，不同神经退行性疾病之间RTN4浓度的比较分析显示，AD患者的RTN4A浓度最高，且AD与PD组、AD与MS组之间存在统计学显著差异。该蛋白脑脊液水平升高与AD以及PD患者的Tau和pTau181蛋白相关。
我们的研究揭示了RTN4在神经退行性疾病鉴别诊断中以前未被发现的临床应用价值。
