Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC.
Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC.
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DOI：
10.1186/s40478-018-0508-2
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发表时间：
2018-02-09
影响因子：
7.1
通讯作者：
Caughey B
中科院分区：
文献类型：
--
作者：
Groveman BR;Orrù CD;Hughson AG;Raymond LD;Zanusso G;Ghetti B;Campbell KJ;Safar J;Galasko D;Caughey B
突触核蛋白病（如帕金森病和路易体痴呆）的诊断和治疗将通过α-突触核蛋白（αSynD）致病性疾病相关形式的检测方法的可用性得到帮助，这些检测方法对于分析可获得的诊断标本具有足够的灵敏度、特异性和实用性。最近的两项αSynD种子扩增试验为患者脑脊液中αSynD的超灵敏和特异性检测提供了第一个原型。这些原型测定需要5-13天才能进行。在这里，我们描述了一种改进的α-突触核蛋白真实的时间振荡诱导转换（αSyn RT-QuIC）测定法，其具有与先前测定法相似的灵敏度和特异性，但可以在1-2天内进行定量。对29例突触核蛋白病病例[12例帕金森病和17例路易体痴呆]和31例非突触核蛋白病对照（包括16例阿尔茨海默病）的脑脊液进行盲法分析，迄今为止，该试验的诊断敏感性为93%，特异性为100%。终点稀释分析允许定量脑脊液样本中αSynD接种活性的相对量，并在低至0.2 μL的样本中进行检测。这些结果证实脑脊液中存在αSynD接种活性。我们还证明，它可以快速检测和定量，即使在早期症状阶段的突触核蛋白病。本文的在线版本（10.1186/s40478-018-0508-2）包含补充材料，可供授权用户使用。
The diagnosis and treatment of synucleinopathies such as Parkinson disease and dementia with Lewy bodies would be aided by the availability of assays for the pathogenic disease-associated forms of α-synuclein (αSynD) that are sufficiently sensitive, specific, and practical for analysis of accessible diagnostic specimens. Two recent αSynD seed amplification tests have provided the first prototypes for ultrasensitive and specific detection of αSynD in patients’ cerebrospinal fluid. These prototypic assays require 5–13 days to perform. Here, we describe an improved α-synuclein real time quaking-induced conversion (αSyn RT-QuIC) assay that has similar sensitivity and specificity to the prior assays, but can be performed in 1–2 days with quantitation. Blinded analysis of cerebrospinal fluid from 29 synucleinopathy cases [12 Parkinson’s and 17 dementia with Lewy bodies] and 31 non-synucleinopathy controls, including 16 Alzheimer’s cases, yielded 93% diagnostic sensitivity and 100% specificity for this test so far. End-point dilution analyses allowed quantitation of relative amounts of αSynD seeding activity in cerebrospinal fluid samples, and detection in as little as 0.2 μL. These results confirm that αSynD seeding activity is present in cerebrospinal fluid. We also demonstrate that it can be rapidly detected, and quantitated, even in early symptomatic stages of synucleinopathy. The online version of this article (10.1186/s40478-018-0508-2) contains supplementary material, which is available to authorized users.
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影响因子：
6.4
作者：
Orrú CD;Wilham JM;Raymond LD;Kuhn F;Schroeder B;Raeber AJ;Caughey B
通讯作者：
Caughey B
DOI：
10.1016/j.bbrc.2008.01.140
发表时间：
2008-04-11
影响因子：
3.1
作者：
Koo, Hyun-Jung;Lee, Hak-Joo;Im, Hana
通讯作者：
Im, Hana
影响因子：
38.1
作者：
Grossman, Murray
通讯作者：
Grossman, Murray
影响因子：
29
作者：
Bongianni, Matilde;Orru, Christina;Zanusso, Gianluigi
通讯作者：
Zanusso, Gianluigi
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影响因子：
11.2
作者：
Foutz A;Appleby BS;Hamlin C;Liu X;Yang S;Cohen Y;Chen W;Blevins J;Fausett C;Wang H;Gambetti P;Zhang S;Hughson A;Tatsuoka C;Schonberger LB;Cohen ML;Caughey B;Safar JG
通讯作者：
Safar JG