Blinded RT-QuIC Analysis of α-Synuclein Biomarker in Skin Tissue From Parkinson's Disease Patients.
Blinded RT-QuIC Analysis of α-Synuclein Biomarker in Skin Tissue From Parkinson's Disease Patients.
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DOI：
10.1002/mds.28242
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Kanthasamy AG
中科院分区：
文献类型：
--
作者：
Manne S;Kondru N;Jin H;Serrano GE;Anantharam V;Kanthasamy A;Adler CH;Beach TG;Kanthasamy AG
PD中未满足的临床需求是鉴定用于诊断的生物标志物，优选地在外周可接近的组织如皮肤中。免疫组织化学研究已经在PD患者的皮肤活检中检测到病理性α-突触核蛋白，尽管灵敏度需要提高。我们的研究提供了PD患者皮肤中存在的病理性α-突触核蛋白的超灵敏检测，因此皮肤中的病理性α-突触核蛋白可能是PD的潜在生物标志物。实时振荡诱导转化试验用于检测人皮肤组织中存在的病理性α-突触核蛋白。此外，我们优化了这种超灵敏和特异性的检测方法，用于皮肤组织的冷冻和福尔马林固定石蜡包埋切片。我们确定了存在于来自尸检受试者的皮肤中的aSyn的接种动力学，所述尸检受试者由来自25个PD和25个对照的冷冻皮肤组织以及来自12个PD和12个对照的福尔马林固定的石蜡包埋的皮肤切片组成。在一项对尸检受试者皮肤组织的盲法研究中，我们使用冷冻皮肤组织正确识别了24/25例PD和24/25例对照（96%灵敏度和96%特异性），而使用福尔马林固定石蜡包埋皮肤切片正确识别了9/12例PD和10/12例对照（75%灵敏度和83%特异性）。我们的盲法研究结果清楚地表明，通过检测病理性α-突触核蛋白，使用皮肤组织进行PD临床诊断的可行性。此外，这项外周生物标志物发现研究可能在检测皮肤样本中的错误折叠蛋白质作为纵向进展标志物方面具有更广泛的翻译价值。
An unmet clinical need in PD is to identify biomarkers for diagnosis, preferably in peripherally accessible tissues such as skin. Immunohistochemical studies have detected pathological α-synuclein in skin biopsies from PD patients albeit sensitivity needs to be improved. Our study provides the ultrasensitive detection of pathological α-synuclein present in the skin of PD patients and thus pathological α-synuclein in skin could be a potential biomarker for PD. The real-time quaking-induced conversion assay was used to detect pathological α-synuclein present in human skin tissues. Further, we optimized this ultra-sensitive and specific assay for both frozen and formalin-fixed paraffin-embedded sections of skin tissues. We determined the seeding kinetics of the aSyn present in the skin from autopsied subjects consisting of frozen skin tissues from 25 PD and 25 controls and formalin-fixed paraffin-embedded skin sections from 12 PD and 12 controls. In a blinded study of skin tissues from autopsied subjects, we correctly identified 24/25 PD and 24/25 controls using frozen skin tissues (96% sensitivity and 96% specificity) compared to 9/12 PD and 10/12 controls using formalin-fixed paraffin-embedded skin sections (75% sensitivity and 83% specificity). Our blinded study results clearly demonstrate the feasibility of using skin tissues for clinical diagnosis of PD by detecting pathological α-synuclein. Moreover, this peripheral biomarker discovery study may have broader translational value in detecting misfolded proteins in skin samples as a longitudinal progression marker.
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影响因子：
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作者：
Cersosimo MG
通讯作者：
Cersosimo MG
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Dickson DW
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