α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson's disease from multiple system atrophy.
α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson's disease from multiple system atrophy.
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用神经元和少突胶质细胞标记物免疫共沉淀的血中α-突触核蛋白可区分帕金森氏病和多系统萎缩。
DOI：
10.1007/s00401-021-02324-0
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发表时间：
2021-09
影响因子：
12.7
通讯作者：
Bitan G
中科院分区：
文献类型：
--
作者：
Dutta S;Hornung S;Kruayatidee A;Maina KN;Del Rosario I;Paul KC;Wong DY;Duarte Folle A;Markovic D;Palma JA;Serrano GE;Adler CH;Perlman SL;Poon WW;Kang UJ;Alcalay RN;Sklerov M;Gylys KH;Kaufmann H;Fogel BL;Bronstein JM;Ritz B;Bitan G
帕金森病（PD）和非典型帕金森综合征的诊断是困难的，由于缺乏可靠的，容易获得的生物标志物。多系统萎缩（MSA）是一种突触核蛋白病，其症状通常与PD重叠。通过使用CNS标志物的免疫沉淀从血液中分离的外泌体提供了进入脑生物化学的窗口，并且可以帮助区分PD和MSA。因此，我们询问此类外泌体中的α-突触核蛋白（α-syn）是否可以区分健康个体、PD患者和MSA患者。我们在两个独立的队列中使用神经元和少突胶质细胞标志物通过免疫沉淀从这三组的血清或血浆中分离外泌体，并使用电化学发光ELISA测量这些外泌体中的α-syn。在两个队列中，与PD组相比，对照组的α-syn浓度显著较低，MSA组显著较高。与假定的神经元外泌体相比，假定的少突胶质细胞外泌体中的α-syn浓度之间的比率是区分PD和MSA的特别敏感的生物标志物。将该比率与α-syn浓度本身和总外泌体浓度相结合，在发现队列上训练的多项逻辑模型将PD与MSA分开，AUC = 0.902，当应用于独立验证队列时，对应于89.8%的灵敏度和86.0%的特异性。数据表明，使用CNS标志物免疫沉淀的血液外泌体中测量α-syn的微创血液检测可以以高灵敏度和特异性区分PD患者和MSA患者。未来的优化和验证的数据，由其他团体将允许这种策略成为一个可行的诊断测试突触核蛋白病。
The diagnosis of Parkinson’s disease (PD) and atypical parkinsonian syndromes is difficult due to the lack of reliable, easily accessible biomarkers. Multiple system atrophy (MSA) is a synucleinopathy whose symptoms often overlap with PD. Exosomes isolated from blood by immunoprecipitation using CNS markers provide a window into the brain’s biochemistry and may assist in distinguishing between PD and MSA. Thus, we asked whether α-synuclein (α-syn) in such exosomes could distinguish among healthy individuals, patients with PD, and patients with MSA. We isolated exosomes from the serum or plasma of these three groups by immunoprecipitation using neuronal and oligodendroglial markers in two independent cohorts and measured α-syn in these exosomes using an electrochemiluminescence ELISA. In both cohorts, α-syn concentrations were significantly lower in the control group and significantly higher in the MSA group compared to the PD group. The ratio between α-syn concentrations in putative oligodendroglial exosomes compared to putative neuronal exosomes was a particularly sensitive biomarker for distinguishing between PD and MSA. Combining this ratio with the α-syn concentration itself and the total exosome concentration, a multinomial logistic model trained on the discovery cohort separated PD from MSA with an AUC = 0.902, corresponding to 89.8% sensitivity and 86.0% specificity when applied to the independent validation cohort. The data demonstrate that a minimally invasive blood test measuring α-syn in blood exosomes immunoprecipitated using CNS markers can distinguish between patients with PD and patients with MSA with high sensitivity and specificity. Future optimization and validation of the data by other groups would allow this strategy to become a viable diagnostic test for synucleinopathies.
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影响因子：
15.1
作者：
Danzer KM;Kranich LR;Ruf WP;Cagsal-Getkin O;Winslow AR;Zhu L;Vanderburg CR;McLean PJ
通讯作者：
McLean PJ
影响因子：
9.9
作者：
Goetzl, Edward J.;Boxer, Adam;Kapogiannis, Dimitrios
通讯作者：
Kapogiannis, Dimitrios
影响因子：
5.3
作者：
Emmanouilidou, Evangelia;Melachroinou, Katerina;Vekrellis, Kostas
通讯作者：
Vekrellis, Kostas
影响因子：
14.5
作者：
Alcalay, Roy N.;Levy, Oren A.;Zhang, Xiaokui
通讯作者：
Zhang, Xiaokui
影响因子：
4.6
作者：
Foulds PG;Diggle P;Mitchell JD;Parker A;Hasegawa M;Masuda-Suzukake M;Mann DM;Allsop D
通讯作者：
Allsop D