Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers.
Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers.
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DOI：
10.3389/fnagi.2014.00248
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发表时间：
2014
影响因子：
4.8
通讯作者：
El-Agnaf OM
中科院分区：
文献类型：
--
作者：
Aasly JO;Johansen KK;Brønstad G;Warø BJ;Majbour NK;Varghese S;Alzahmi F;Paleologou KE;Amer DA;Al-Hayani A;El-Agnaf OM
富含亮氨酸的重复蛋白激酶2基因突变是常染色体显性遗传性帕金森病(PD)的最常见原因。为了解有症状和无症状富含亮氨酸重复蛋白重复蛋白2突变携带者脑脊液中α-突触核蛋白寡聚体的水平，我们采用酶联免疫吸附试验检测了脑脊液中α-突触核蛋白的总形式和寡聚形式。脑脊液样本来自33名携带富含亮氨酸重复蛋白2突变的挪威人：13例临床诊断为帕金森病患者，20例健康、无症状的富含亮氨酸重复蛋白2突变携带者。我们还包括35名散发性帕金森病(SPD)患者和42名年龄匹配的健康对照。与健康对照组相比，携带富含亮氨酸重复蛋白K2基因突变的健康个体(n=20；P<；0.0079)和SPD组(n=35；P<；0.003)的脑脊液α-突触核蛋白寡聚体水平显著升高。在无症状亮氨酸重复蛋白2突变携带者中，α-突触核蛋白寡聚体增加的敏感性为63.0%，特异性为74.0%，曲线下面积为0.66；SPD患者的敏感性为65.0%，特异性为83.0%，曲线下面积为0.74。脑脊液中α-突触核蛋白寡聚体水平与病情严重程度和病程呈负相关。我们的研究表明，脑脊液中α-突触核蛋白寡聚体的定量检测对帕金森病的诊断和高危个体的症状前筛查具有潜在的价值。
Mutations in the leucine-rich repeat kinase 2 gene are the most common cause of autosomal dominant Parkinson’s disease (PD). To assess the cerebrospinal fluid (CSF) levels of α-synuclein oligomers in symptomatic and asymptomatic leucine-rich repeat kinase 2 mutation carriers, we used enzyme-linked immunosorbent assays (ELISA) to investigate total and oligomeric forms of α-synuclein in CSF samples. The CSF samples were collected from 33 Norwegian individuals with leucine-rich repeat kinase 2 mutations: 13 patients were clinically diagnosed with PD and 20 patients were healthy, asymptomatic leucine-rich repeat kinase 2 mutation carriers. We also included 35 patients with sporadic PD (sPD) and 42 age-matched healthy controls. Levels of CSF α-synuclein oligomers were significantly elevated in healthy asymptomatic individuals carrying leucine-rich repeat kinase 2 mutations (n = 20; P < 0.0079) and in sPD group (n = 35; P < 0.003) relative to healthy controls. Increased α-synuclein oligomers in asymptomatic leucine-rich repeat kinase 2 mutation carriers showed a sensitivity of 63.0% and a specificity of 74.0%, with an area under the curve of 0.66, and a sensitivity of 65.0% and a specificity of 83.0%, with an area under the curve of 0.74 for sPD cases. An inverse correlation between CSF levels of α- synuclein oligomers and disease severity and duration was observed. Our study suggests that quantification of α-synuclein oligomers in CSF has potential value as a tool for PD diagnosis and presymptomatic screening of high-risk individuals.