α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson's Disease Patients and Correlate with Disease Severity.
α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson's Disease Patients and Correlate with Disease Severity.
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DOI：
10.3389/fnmol.2018.00053
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发表时间：
2018
影响因子：
4.8
通讯作者：
Bonuccelli U
中科院分区：
文献类型：
--
作者：
Daniele S;Frosini D;Pietrobono D;Petrozzi L;Lo Gerfo A;Baldacci F;Fusi J;Giacomelli C;Siciliano G;Trincavelli ML;Franzoni F;Ceravolo R;Martini C;Bonuccelli U
神经退行性疾病 (ND) 的特点是大脑和外周组织中特定蛋白质的异常积累/错误折叠，主要是 α-突触核蛋白 (α-syn)、β-淀粉样蛋白 1-42 (Aβ1-42) 和 tau。除了寡聚物之外，α-syn与Aβ或tau相互作用的作用也逐渐显现。然而，尽管进行了深入的研究，NDs 还没有公认的用于生化诊断的外周标志物。在这方面，红细胞（RBC）正在成为研究衰老相关病理学的有效外周模型。在此，招募了一小群 (N = 28) 帕金森病 (PD) 患者和年龄匹配的对照组，以检测红细胞中 α-syn（总和寡聚）、Aβ1-42 和 tau（总和磷酸化）的含量。此外，通过在相同细胞中进行免疫共沉淀/蛋白质印迹来探索 α-syn 与 tau 和 Aβ1-42 关联的存在，并通过免疫酶测定进行定量确认。首次证明 PD 患者在外周组织中表现出与 Aβ1-42 和 tau 的 α-syn 异质复合物；有趣的是，与健康对照 (HC) 相比，PD 受试者的 α-syn-Aβ1-42 浓度有所增加，并且与疾病严重程度和运动缺陷直接相关。此外，PD 受试者的总 α-syn 水平下降，并且与他们的运动缺陷呈负相关。最后，在入组患者的红细胞中观察到寡聚-α-syn 和磷酸化-tau 的增加。三个参数（总 α-syn、磷酸化 tau 和 α-syn-Aβ1-42 浓度）的组合为区分 PD 患者和对照组提供了最合适的预测指数。尽管如此，仍需进一步研究，总体而言，这些数据表明红细胞中的 α-syn 异质聚集体可作为 PD 诊断的假定工具。
Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ1–42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N = 28) of patients affected by Parkinson’s disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ1–42 and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ1–42 was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ1–42 and tau in peripheral tissues; interestingly, α-syn-Aβ1–42 concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ1–42 concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD.
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