多发性硬化症中的脑脊液突触生物标志物与认知障碍
CSF synaptic biomarkers and cognitive impairment in multiple sclerosis.
作者信息
Barba Lorenzo, Gaetani Lorenzo, Sperandei Silvia, Di Sabatino Elena, Abu-Rumeileh Samir, Halbgebauer Steffen, Oeckl Patrick, Steinacker Petra, Parnetti Lucilla, Di FIlippo Massimiliano, Otto Markus
机构信息
Department of Neurology, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle (Saale), Germany.
Section of Neurology, Department of Medicine and Surgery, University of Perugia, Piazzale Gambuli 1, 06129, Perugia, Italy.
出版信息
J Neurol. 2024 Dec 21;272(1):85. doi: 10.1007/s00415-024-12851-x.
BACKGROUND
People with multiple sclerosis (PwMS) experience various degrees of cognitive impairment (CI). Synaptic dysfunction may contribute to CI in PwMS but cerebrospinal fluid (CSF) synaptic biomarkers are unexplored in MS.
OBJECTIVE
To assess the role of CSF synaptosomal-associated protein 25 (SNAP-25), β-synuclein, neurogranin and neurofilament light chain protein (NfL) in patients with early relapsing MS with and without CI.
METHODS
We measured CSF SNAP-25, β-synuclein, and neurogranin in 48 untreated PwMS and 50 controls with other neurological diseases (ONDs) and tested their associations with neuropsychological and MRI data.
RESULTS
CSF synaptic protein levels did not discriminate between MS subjects and patients with ONDs, with only SNAP-25 values being slightly increased in MS (p = 0.009). CSF synaptic markers were positively correlated with each other and with CSF NfL. Moreover, lower biomarker levels were found to be correlated with longer disease duration and lower brain volumes (especially of the thalamus). Moreover, we found significantly lower CSF SNAP-25 (p = 0.025), β-synuclein (p = 0.044), and neurogranin (p = 0.007) levels in PwMS with vs. without domain-specific cognitive impairment.
CONCLUSION
Lower CSF synaptic biomarker levels were found in PwMS with longer disease duration and lower brain volumes and may identify PwMS at risk of CI.
背景
多发性硬化症患者（PwMS）会经历不同程度的认知障碍（CI）。突触功能障碍可能导致PwMS患者出现认知障碍，但脑脊液（CSF）中的突触生物标志物在多发性硬化症中尚未得到研究。
目的
评估脑脊液中突触体相关蛋白25（SNAP-25）、β-突触核蛋白、神经颗粒蛋白和神经丝轻链蛋白（NfL）在有无认知障碍的早期复发型多发性硬化症患者中的作用。
方法
我们测量了48例未经治疗的PwMS患者和50例患有其他神经系统疾病（ONDs）的对照者脑脊液中的SNAP-25、β-突触核蛋白和神经颗粒蛋白，并测试了它们与神经心理学和MRI数据之间的关联。
结果
脑脊液中的突触蛋白水平在MS患者和ONDs患者之间没有差异，只有MS患者的SNAP-25值略有升高（p = 0.009）。脑脊液中的突触标志物相互之间以及与脑脊液中的NfL呈正相关。此外，发现较低的生物标志物水平与较长的病程和较小的脑容量（尤其是丘脑）相关。此外，我们发现，与无特定领域认知障碍的PwMS患者相比，有特定领域认知障碍的PwMS患者脑脊液中的SNAP-25（p = 0.025）、β-突触核蛋白（p = 0.044）和神经颗粒蛋白（p = 0.007）水平显著降低。
结论
在病程较长、脑容量较小的PwMS患者中发现脑脊液突触生物标志物水平较低，这可能有助于识别有认知障碍风险的PwMS患者。
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