关键词: alpha‐synuclein biomarker protein misfolding cyclic amplification (PMCA) real‐time quaking‐induced conversion (RT‐QuIC) synucleinopathy

来  源:   DOI:10.1002/mdc3.13710   PDF(Pubmed)

Abstract:
UNASSIGNED: Real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) have been developed to detect minute amounts of amyloidogenic proteins via amplification techniques and have been used to detect misfolded α-synuclein (αSyn) aggregates in the cerebrospinal fluid (CSF) and other source materials of patients with Parkinson\'s Disease and other synucleinopathies.
UNASSIGNED: The aim of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of αSyn seed amplification assays (αSyn-SAAs), including RT-QuIC and PMCA, using CSF as source material to differentiate synucleinopathies from controls.
UNASSIGNED: The electronic MEDLINE database PubMed was searched for relevant articles published until June 30, 2022. Study quality assessment was performed using the QUADAS-2 toolbox. A random effects bivariate model was exploited for data synthesis.
UNASSIGNED: Our systematic review identified 27 eligible studies according to the predefined inclusion criteria, of which 22 were included in the final analysis. Overall, 1855 patients with synucleinopathies and 1378 non-synucleinopathies as control subjects were included in the meta-analysis. The pooled sensitivity and specificity to differentiate synucleinopathies from controls with αSyn-SAA were 0.88 (95% CI, 0.82-0.93) and 0.95 (95% CI, 0.92-0.97), respectively. Evaluating the diagnostic performance of RT-QuIC in a subgroup analysis for the detection of patients with multiple system atrophy the pooled sensitivity decreased to 0.30 (95% CI, 0.11-0.59).
UNASSIGNED: While our study clearly demonstrated a high diagnostic performance of RT-QuIC and PMCA for differentiating synucleinopathies with Lewy bodies from controls, results for the diagnosis of multiple system atrophy were less robust.
摘要:
已开发出实时震颤诱导的转换(RT-QuIC)和蛋白质错误折叠循环扩增(PMCA),以通过扩增技术检测微量的淀粉样蛋白,并已用于检测错误折叠的α-突触核蛋白(αSyn)聚集体在帕金森病和其他突触核蛋白病患者的脑脊液(CSF)和其他来源材料中。
本系统综述和荟萃分析的目的是评估αSyn种子扩增测定(αSyn-SAAs)的诊断准确性,包括RT-QuIC和PMCA,使用CSF作为来源材料来区分突触核蛋白病与对照。
在电子MEDLINE数据库PubMed中搜索了直到2022年6月30日发布的相关文章。使用QUADAS-2工具箱进行研究质量评估。采用随机效应双变量模型进行数据综合。
我们的系统评价根据预定义的纳入标准确定了27项符合条件的研究,其中22人被列入最终分析。总的来说,1855例突触核蛋白病患者和1378例非突触核蛋白病患者作为对照受试者被纳入荟萃分析。用αSyn-SAA区分突触核蛋白病与对照的合并敏感性和特异性分别为0.88(95%CI,0.82-0.93)和0.95(95%CI,0.92-0.97),分别。在检测多系统萎缩患者的亚组分析中评估RT-QuIC的诊断性能,合并敏感性降至0.30(95%CI,0.11-0.59)。
虽然我们的研究清楚地证明了RT-QuIC和PMCA在区分路易体突触核蛋白病变与对照组方面的高诊断性能,多系统萎缩的诊断结果不太可靠。
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