Maass Fabian, Canaslan Sezgi, van Riesen Christoph, Hermann Peter, Schmitz Matthias, Schulte Claudia, Brockmann Kathrin, Synofzik Matthis, Bähr Mathias, Zerr Inga
Department of Neurology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
J Neurol. 2024 Dec 12;272(1):52. doi: 10.1007/s00415-024-12747-w.
It is well known that myelin disruption and neuroinflammation are early and distinct pathological hallmarks in multiple system atrophy (MSA) as well as in idiopathic Parkinson's disease and in other atypical Parkinsonian syndromes. The objective of this study was to assess the value of non-neuronal biomarker candidates that reflect myelin disruption and neuroinflammation.
Myelin basic protein (MBP) and the soluble form of TREM2 were quantified in a comprehensive movement disorder cohort from two different neurological centers, comprising a total of 171 CSF samples. Commercially available ELISA systems were employed for quantification.
The results of the MBP analysis revealed a significant increase in cerebrospinal fluid (CSF) MBP levels in all atypical Parkinsonian conditions compared to PD. This differentiation was more pronounced in the MSA-c subtype compared to MSA-p. Receiver operating characteristic (ROC) analysis revealed a significant discrimination between PD and MSA (p = 0.032, AUC = 0.70), PD and DLB (p = 0.006, AUC = 0.79) and PD and tauopathies (p = 0.006, AUC = 0.74). The results of the TREM2 analysis demonstrated no significant differences between the PD and atypical Parkinsonian groups if not adjusted for confounders. After adjusting for age, sex, and disease duration, the PD group exhibited significantly higher TREM2 levels compared to the DLB group (p = 0.002).
In conclusion, MBP, but not TREM2, is elevated in the CSF of not only MSA but in all atypical Parkinsonian conditions compared to idiopathic Parkinson's disease. This highlights the value of the evaluation of myelin/oligodendrocyte-associated markers in neurodegenerative movement disorders.
众所周知，髓鞘破坏和神经炎症是多系统萎缩（MSA）、特发性帕金森病及其他非典型帕金森综合征早期且明显的病理特征。本研究的目的是评估反映髓鞘破坏和神经炎症的非神经元生物标志物候选物的价值。
在来自两个不同神经中心的综合运动障碍队列中，对髓鞘碱性蛋白（MBP）和可溶性TREM2进行定量分析，共包括171份脑脊液样本。采用市售酶联免疫吸附测定（ELISA）系统进行定量分析。
MBP分析结果显示，与帕金森病（PD）相比，所有非典型帕金森病情况下脑脊液（CSF）中MBP水平均显著升高。与MSA-p相比，这种差异在MSA-c亚型中更为明显。受试者操作特征（ROC）分析显示，PD与MSA之间存在显著差异（p = 0.032，曲线下面积[AUC] = 0.70），PD与路易体痴呆（DLB）之间存在显著差异（p = 0.006，AUC = 0.79），PD与tau蛋白病之间存在显著差异（p = 0.00,6，AUC = 0.74）。TREM2分析结果表明，如果不调整混杂因素，PD组与非典型帕金森病组之间无显著差异。在调整年龄、性别和病程后，与DLB组相比，PD组TREM2水平显著更高（p = 0.002）。
总之，与特发性帕金森病相比，不仅MSA，而且所有非典型帕金森病情况下脑脊液中MBP水平均升高，而TREM2水平无升高。这突出了评估神经退行性运动障碍中髓鞘/少突胶质细胞相关标志物的价值。
