Biomarkers for parkinsonian disorders in CNS-originating extracellular vesicles

总结 许多帕金森氏症病例，甚至更多的非典型帕金森氏症，被误诊。 误诊不仅会给患者、家属和护理人员带来巨大的压力和焦虑， 这是发展这些疾病的有效疗法的主要障碍。最近，我们证明了 使用免疫沉淀法从血清或血浆中免疫沉淀细胞外囊泡（EV）中的α-突触核蛋白浓度， 少突胶质细胞和神经元标记物，特别是α-突触核蛋白浓度之间的比率， 两种类型的EV，是区分帕金森病和多系统的敏感生物标志物 萎缩这种液体活检方法只需要微创抽血， 在开发这些疾病的诊断测试方面取得了进展。在这里，我们建议在这些最近的基础上， 通过构建生物标志物面板，包括几个额外的候选标志物，并应用面板， 另外两种非典型帕金森综合征-进行性核上性麻痹和皮质基底综合征。 本研究的血清样本将从几个国家生物储存库以及当地采集， 前瞻性地，在专家诊所。该研究设计强调在前两年内的生物标志物分析， 诊断，并在前驱突触核蛋白病，以测试的效用时，它是最需要的生物标志物面板。 该项目的另一个目标是开发验证电动汽车细胞起源的方法，这是一个紧迫的问题。 外地未满足的需求。该项目的成功将推动生物标志物的研究， CNS疾病使用微创液体活检，可以转化为临床使用在不久的将来。

Summary Many cases of Parkinson’s disease, and even more so atypical parkinsonian disorders, are misdiagnosed. Misdiagnosis not only causes high stress and anxiety to patients, their families, and their caregivers, but also is a major impediment to development of effective therapy for these diseases. Recently, we have demonstrated that the α-synuclein concentration in extracellular vesicles (EVs) immunoprecipitated from serum or plasma using oligodendroglial and neuronal markers, and in particular the ratio between the α-synuclein concentrations in the two types of EVs, is a sensitive biomarker for distinguishing between Parkinson’s disease and multiple system atrophy. This liquid biopsy approach requires only a minimally invasive blood draw and could lead to a major advancement in developing diagnostic tests for these diseases. Here, we propose to build upon these recent findings by constructing a biomarker panel, including several additional candidate markers, and apply the panel to two additional atypical parkinsonian syndromes—progressive supranuclear palsy and corticobasal syndrome. Serum samples for the study will be obtained from several national biorepositories as well as collected locally, prospectively, in expert clinics. The study design emphasizes biomarker analysis within the first two years of diagnosis, and in prodromal synucleinopathy, to test the utility of the biomarker panel when it is most needed. An additional goal of the project is to develop methodology for validating the cellular origin of the EVs, an urgent unmet need in the field. Success of the project will lead both to an advancement of research on biomarkers for CNS diseases using a minimally invasive liquid biopsy that can be translated into clinical use in the near future.