CSF biomarkers and clinical progression of Parkinson disease
CSF biomarkers and clinical progression of Parkinson disease
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DOI：
10.1212/wnl.0000000000001098
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发表时间：
2015-01-06
期刊：
影响因子：
9.9
通讯作者：
Hansson, Oskar
中科院分区：
文献类型：
--
作者：
Hall, Sara;Surova, Yulia;Hansson, Oskar
目的：调查是否某些CSF生物标志物在基线可以预测未来的进展，运动症状和认知功能下降的帕金森病（PD）患者（PD）。方法：患者和对照组从瑞典南部的医院招募的前瞻性和纵向的瑞典生物学研究的一部分。在本研究中，我们纳入了42例PD患者和69例对照组，这些患者在基线时进行了临床评估和腰椎穿刺。分析基线CSF样本的α-突触核蛋白（α Syn）、β-淀粉样蛋白1-42（A β（42））、tau、磷酸化tau和神经丝光。使用多变量模型对基线CSF标志物与2年随访后临床特征变化之间的关系进行了研究，该模型调整了年龄、性别、疾病持续时间和左旋多巴等效日剂量。PD组中较高水平的aSyn与运动症状的进展和2年内的认知下降相关，由aSyn与Hoehn和Yahr的变化之间的显著关系表明，（β = 0.394，p = 0.043），统一帕金森病评定量表，第III部分（CRISPR-III）（β = 0.449，p = 0.013），定时启动和启动（β = 0.406，p = 0.023），以及认知速度快速测试（β = 0.423，p = 0.018）。较低水平的A β（42）与延迟记忆回忆的表现恶化相关（F = 5.834，p = 0.022）。最后，高水平的磷酸化tau蛋白与运动症状恶化相关（β-淀粉样蛋白-III，β = 0.350，p = 0.045; Hoehn和Yahr，β = 0.366，p = 0.038）。结论：我们发现了基线时较高水平的aSyn与PD中2年内运动症状和认知速度恶化之间存在联系的证据。增加的α-Syn可能是PD中更强烈的突触变性的标志。结果表明，皮质淀粉样病变（低CSF A β（42））与记忆力下降有关。
Objective: To investigate whether certain CSF biomarkers at baseline can predict future progression of motor symptoms and cognitive decline in patients with Parkinson disease (PD).Methods: Patients and controls were recruited from hospitals in southern Sweden as part of the prospective and longitudinal Swedish BioFinder Study. In the present study, we included 42 patients with PD and 69 controls who had clinical assessment and lumbar puncture at baseline. Baseline CSF samples were analyzed for alpha-synuclein (alpha Syn), beta-amyloid 1-42 (A beta(42)), tau, phosphorylated tau, and neurofilament light. Associations between CSF markers at baseline and change in clinical characteristics after 2 years of follow-up were investigated using multivariate models adjusting for age, sex, disease duration, and levodopa-equivalent daily dose.Results: Higher levels of aSyn within the PD group were associated with progression of motor symptoms and cognitive decline over 2 years, indicated by significant relationships between aSyn and change in Hoehn and Yahr (beta = 0.394, p = 0.043), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (beta = 0.449, p = 0.013), Timed Up and Go (beta = 0.406, p = 0.023), and A Quick Test of Cognitive Speed (beta = 0.423, p = 0.018). Lower levels of A beta(42) were associated with worsening of performance on delayed memory recall (F = 5.834, p = 0.022). Finally, high levels of phosphorylated tau were associated with worsening in motor symptoms (UPDRS-III, beta = 0.350, p = 0.045; Hoehn and Yahr, beta = 0.366, p = 0.038).Conclusion: We found evidence of a link between higher levels of aSyn at baseline and worsening of motor symptoms and cognitive speed over 2 years in PD. Increased alpha Syn might be a marker of more intense synaptic degeneration in PD. The results indicate that cortical amyloid pathology (low CSF A beta(42)) is associated with memory decline.