Skin α-synuclein deposition is considered a potential biomarker for Parkinson’s disease (PD). Real-time quaking-induced conversion (RT-QuIC) is a novel, ultrasensitive, and efficient seeding assay that enables the detection of minute amounts of α-synuclein aggregates. We aimed to determine the diagnostic accuracy, reliability, and reproducibility of α-synuclein RT-QuIC assay of skin biopsy for diagnosing PD and to explore its correlation with clinical markers of PD in a two-center inter-laboratory comparison study. Patients with clinically diagnosed PD (n = 34), as well as control subjects (n = 30), underwent skin punch biopsy at multiple sites (neck, lower back, thigh, and lower leg). The skin biopsy samples (198 in total) were divided in half to be analyzed by RT-QuIC assay in two independent laboratories. The α-synuclein RT-QuIC assay of multiple skin biopsies supported the clinical diagnosis of PD with a diagnostic accuracy of 88.9% and showed a high degree of inter-rater agreement between the two laboratories (92.2%). Higher α-synuclein seeding activity in RT-QuIC was shown in patients with longer disease duration and more advanced disease stage and correlated with the presence of REM sleep behavior disorder, cognitive impairment, and constipation. The α-synuclein RT-QuIC assay of minimally invasive skin punch biopsy is a reliable and reproducible biomarker for Parkinson’s disease. Moreover, α-synuclein RT-QuIC seeding activity in the skin may serve as a potential indicator of progression as it correlates with the disease stage and certain non-motor symptoms.

皮肤 α-突触核蛋白沉积被认为是帕金森病 (PD) 的潜在生物标志物。实时震动诱导转化 (RT-QuIC) 是一种新颖、超灵敏且高效的接种测定，能够检测微量的 α-突触核蛋白聚集体。我们的目的是确定皮肤活检 α-突触核蛋白 RT-QuIC 检测诊断 PD 的准确性、可靠性和重现性，并在一项两中心实验室间比较研究中探讨其与 PD 临床标志物的相关性。临床诊断为 PD 的患者 ( n = 34) 以及对照受试者 ( n = 30) 在多个部位（颈部、下背部、大腿和小腿）接受了皮肤穿刺活检。皮肤活检样本（总共 198 个）被分成两半，在两个独立实验室通过 RT-QuIC 检测进行分析。多个皮肤活检的 α-突触核蛋白 RT-QuIC 检测支持 PD 的临床诊断，诊断准确率为 88.9%，并且两个实验室之间的评估者间高度一致 (92.2%)。在病程较长和疾病阶段较晚期的患者中，RT-QuIC 中的 α-突触核蛋白播种活性较高，并且与 REM 睡眠行为障碍、认知障碍和便秘的存在相关。微创皮肤穿刺活检的 α-突触核蛋白 RT-QuIC 检测是帕金森病可靠且可重复的生物标志物。此外，皮肤中的 α-突触核蛋白 RT-QuIC 播种活性可能作为进展的潜在指标，因为它与疾病阶段和某些非运动症状相关。