In vivo markers of Parkinson’s disease and dementia with Lewy bodies: current value of the 5G4 α-synuclein antibody
In vivo markers of Parkinson’s disease and dementia with Lewy bodies: current value of the 5G4 α-synuclein antibody
复制标题
帕金森病和路易体痴呆的体内标志物：5G4 α-突触核蛋白抗体的当前值
DOI：
10.1007/s00401-014-1364-1
复制
发表时间：
2014
影响因子：
12.7
通讯作者：
Daniela Berg
中科院分区：
文献类型：
--
作者：
Walter Maetzler;Andrea Pilotto;Anja Apel;Christian Deuschle;Gabriele Kuebart;Sebastian Heinzel;Inga Liepelt-Scarfone;Claudia Schulte;Dorothee Reusch;Erwin Schleicher;Oliver Rothfuss;Anja Schneider;Richard Dodel;Thomas Gasser;Daniela Berg
修订日期：2014年10月29日/接受日期：2014年11月1日/在线发表日期：2014年11月7日© Springer-Verlag柏林海德堡2014年免疫印迹法上仅在DLB个体中发现额外的35 kDa条带。在最近的另一份报告中，同一研究组在7例α-突触核蛋白病患者中的4例中检测到脑脊液（CSF）5G 4 α-突触核蛋白水平升高的趋势[7]。我们首次在大量活体患者中测试了相同的5G 4-Ab（PATHO-Kit，Analytic Jena Roboscreen GmbH，Leipzig，德国）。该研究根据现行临床标准（补充材料）评价了诊断为PD [n= 130，31例痴呆（PDD）]和DLB（n= 36）的患者的血清5G 4和总α-突触核蛋白水平（MONO-试剂盒，同一公司）。在血清中，PD、DLB和健康对照组的平均5G 4 α-突触核蛋白水平相似（n= 101）（表1）。与对照组相比，DLB中的总α-突触核蛋白水平较低（p= 0.001），而所有组中的总/5G 4-α-突触核蛋白比值相似。离群值的单独分析未显示标志物与人口统计学、临床和神经化学常规参数之间的相关性（补充表1）。唯一值得注意的发现是较早的年龄尽管在了解α-突触核蛋白病的分子机制方面取得了很大进展，但转化研究仍在寻找可靠的体内生物标志物。作为这一领域的重要一步，Kovacs等人。[1]2012年发表在该杂志上的一项新的单克隆抗体（5G 4-Ab）的分离，该抗体对累积的错误折叠（但不是生理单体）α-突触核蛋白具有特异性，这是在通过小鼠免疫产生α-突触核蛋白聚集体后发现的。在帕金森病（PD）、路易体痴呆（DLB）和多系统萎缩（MSA）患者的脑组织中的比较免疫组织化学研究中测试该抗体。与现有的免疫组化检测相比，5G 4-Ab显示出更高的灵敏度和特异性。一个
Revised: 29 October 2014/Accepted: 1 November 2014/Published online: 7 November 2014© Springer-Verlag Berlin Heidelberg 2014 additional 35 kDa band on immunoblotting was found only in individuals with DLB. In another recent report, the same group detected a trend towards higher cerebrospinal fluid (CSF) 5G4 α-synuclein levels in four out of seven patients affected by α-synucleinopathies [7]. We tested the same 5G4-Ab for the first time in a large series of living patients (PATHO-Kit, Analytic Jena Roboscreen GmbH, Leipzig, Germany). The study evaluated serum 5G4 and total α-synuclein levels (MONO-kit, same company) in patients with a diagnosis of PD [n= 130, 31 with dementia (PDD)] and DLB (n= 36) according to current clinical criteria (Supplementary material). In the serum, mean 5G4 α-synuclein levels were similar in PD, DLB and healthy controls (n= 101)(Table 1). Total α-synuclein levels were lower in DLB compared to controls (p= 0.001), while the total/5G4-α-synuclein ratio was similar in all groups. Separate analysis of outliers did not show relevant associations between the marker and demographic, clinical and neurochemical routine parameters (Supplementary Table 1). The only remarkable finding was an earlier age atDespite the great advances in understanding the molecular mechanisms involved in α-synucleinopathies, translational research is still looking for a reliable in vivo biomarker. As an important step forward in this field, Kovacs et al.[1] published in this Journal in 2012 the isolation of a new monoclonal antibody (5G4-Ab) specific for accumulated misfolded (but not physiological monomeric) α-synuclein, which was found after generation of α-synuclein aggregates by mice immunization. This antibody was tested in comparative immunohistochemical studies in brain tissue of patients with Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). 5G4-Ab showed higher sensitivity and specificity compared to available immunohistochemical assays. An
影响因子：
1.1
作者：
Unterberger U;Lachmann I;Voigtländer T;Pirker W;Berghoff AS;Flach K;Wagner U;Geneste A;Perret-Liaudet A;Kovacs GG
通讯作者：
Kovacs GG