■为统称为突触核蛋白病(帕金森病[PD],路易体痴呆[DLB],多系统萎缩[MSA],而纯粹的自主神经衰竭[PAF])是一个迫切的未满足的需求。皮肤磷酸化α-突触核蛋白的免疫组织化学检测可能是诊断突触核蛋白病的敏感和特异性临床测试。
■为了评估PD患者皮肤α-突触核蛋白沉积的阳性率,DLB,MSA,和PAF。
■这个盲人,30-site,从2021年2月至2023年3月进行的学术和社区神经病学实践的横断面研究包括40至99岁的临床诊断为PD的患者,DLB,MSA,或PAF基于临床共识标准,并由专家审查小组和40至99岁的对照参与者确认,没有检查发现或症状提示突触核蛋白病或神经退行性疾病的病史。所有参与者都完成了详细的神经系统检查和疾病特异性问卷,并接受了皮肤活检以检测磷酸化的α-突触核蛋白。专家审查小组对病理数据视而不见,确定了最终的参与者诊断。
■用于检测磷酸化α-突触核蛋白的皮肤活检。
■PD患者皮肤α-突触核蛋白的检测率,MSA,DLB,和PAF和没有突触核蛋白病的对照。
■在428名注册参与者中,主要分析中包括343人(平均[SD]年龄,69.5[9.1]岁;男性175[51.0%]);在专家小组审查后,223符合突触核蛋白病的共识标准,120符合对照标准。皮肤活检检测到皮肤磷酸化α-突触核蛋白的比例为92.7%(96个中的89个),98.2%(55个中的54个)有MSA,96.0%(50个中的48个)使用DLB,100%(22个中的22个)有PAF;3.3%(120个中的4个)的对照组检测到皮肤磷酸化的α-突触核蛋白。
■在这项横断面研究中,符合PD临床共识标准的人比例很高,DLB,MSA,并且通过皮肤活检检测到PAF具有磷酸化的α-突触核蛋白。需要在未经选择的临床人群中进行进一步的研究,以外部验证发现并充分表征皮肤活检检测磷酸化α-突触核蛋白在临床护理中的潜在作用。
Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies.
To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF.
This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis.
Skin biopsy for detection of phosphorylated α-synuclein.
Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy.
Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected.
In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.