α-突触核蛋白种籽扩增检测在α-突触核蛋白病中的诊断价值：系统评价和荟萃分析。
Diagnostic value of α-synuclein seeding amplification assays in α-synucleinopathies: A systematic review and meta-analysis.
机构信息
Department of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
Department of Nuclear Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea.
出版信息
Parkinsonism Relat Disord. 2022 Nov;104:99-109. doi: 10.1016/j.parkreldis.2022.10.007. Epub 2022 Oct 19.
INTRODUCTION
Alpha-synuclein(αSyn) aggregates are definite pathological hallmarks of α-synucleinopathies. Seeding amplification assays (SAAs) have been developed to detect trace amounts of αSyn oligomers in vivo.. Herein, we assessed the diagnostic accuracy of the αSyn-SAAs across biospecimens, diagnostic references, methods, and subtypes.
METHODS
A systematic literature search yielded 36 eligible studies for a meta-analysis of the sensitivity and specificity of αSyn-SAAs in patients with α-synucleinopathies(n = 2722) and controls(n = 2278). Pooled sensitivities and specificities with 95% confidence intervals (CIs) were calculated using bivariate random-effects models and a meta-regression analysis was performed.
RESULTS
The summary sensitivity and specificity of αSyn-SAAs positivity for the diagnosis of α-synucleinopathies were 0.88(95% CIs = 0.84-0.91) and 0.95(0.93-0.97), respectively. Two covariates (biospecimen and diagnostic reference) were significant in fitting the meta-regression model (likelihood-ratio test for sensitivity and specificity, p < 0.01, p = 0.01, respectively). Skin αSyn-SAAs exhibited the highest sensitivity 0.92(0.87-0.95), which was not different from that of cerebrospinal fluid (CSF)(0.90(0.86-0.93), p = 0.39). Olfactory mucosa αSyn-SAAs exhibited a lower sensitivity 0.64(0.49-0.76) than those of the other two specimens(p = 0.02, 0.01, compared to CSF and skin, respectively). Application of pathological diagnostic standards were associated with a higher specificity of αSyn-SAAs compared to clinical diagnosis (p < 0.01). The diagnostic sensitivity and specificity of CSF αSyn-SAAs were 0.91(0.87-0.94) and 0.96(0.93-0.98) for Lewy body disease, 0.90(0.79-0.95) and 0.96(0.90-0.98) for prodromal α-synucleinopathies, and 0.63(0.24-0.90) and 0.97(0.93-0.99) for multiple system atrophy.
CONCLUSIONS
αSyn-SAAs are promising in vivo detectors of abnormal αSyn aggregates and may aid the early diagnosis of α-synucleinopathies.
简介
α-突触核蛋白（αSyn）聚集体是α-突触核蛋白病的明确病理标志物。种系扩增检测（SAA）已被开发用于检测体内痕量的αSyn 寡聚物。在此，我们评估了αSyn-SAA 在生物样本、诊断参考、方法和亚型方面的诊断准确性。
方法
系统文献检索产生了 36 项符合荟萃分析的研究，以评估 α-突触核蛋白病患者（n=2722）和对照组（n=2278）中 αSyn-SAA 的敏感性和特异性。使用双变量随机效应模型计算汇总敏感性和特异性以及 95%置信区间（CI），并进行荟萃回归分析。
结果
αSyn-SAA 阳性对 α-突触核蛋白病的诊断综合敏感性和特异性分别为 0.88（95%CI=0.84-0.91）和 0.95（0.93-0.97）。两个协变量（生物样本和诊断参考）在拟合荟萃回归模型中具有显著性（敏感性和特异性似然比检验，p<0.01，p=0.01）。皮肤 αSyn-SAA 的敏感性最高，为 0.92（0.87-0.95），与脑脊液（CSF）的敏感性相同（0.90（0.86-0.93），p=0.39）。嗅觉黏膜 αSyn-SAA 的敏感性较低，为 0.64（0.49-0.76），与另外两种标本相比，差异有统计学意义（p=0.02，0.01，分别与 CSF 和皮肤相比）。与临床诊断相比，应用病理诊断标准与 αSyn-SAA 的特异性较高有关（p<0.01）。CSF αSyn-SAA 对路易体病的诊断敏感性和特异性分别为 0.91（0.87-0.94）和 0.96（0.93-0.98），对前驱期 α-突触核蛋白病的诊断敏感性和特异性分别为 0.90（0.79-0.95）和 0.96（0.90-0.98），对多系统萎缩的诊断敏感性和特异性分别为 0.63（0.24-0.90）和 0.97（0.93-0.99）。
结论
αSyn-SAA 是体内异常 αSyn 聚集物的有前途的检测物，可能有助于 α-突触核蛋白病的早期诊断。
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