In vivo distribution of α-synuclein in multiple tissues and biofluids in Parkinson disease.
In vivo distribution of α-synuclein in multiple tissues and biofluids in Parkinson disease.
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DOI：
10.1212/wnl.0000000000010404
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发表时间：
2020-09-01
期刊：
影响因子：
9.9
通讯作者：
Systemic Synuclein Sampling Study
中科院分区：
文献类型：
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作者：
Chahine LM;Beach TG;Brumm MC;Adler CH;Coffey CS;Mosovsky S;Caspell-Garcia C;Serrano GE;Munoz DG;White CL 3rd;Crary JF;Jennings D;Taylor P;Foroud T;Arnedo V;Kopil CM;Riley L;Dave KD;Mollenhauer B;Systemic Synuclein Sampling Study
系统性突触核蛋白抽样研究(S4)检测了帕金森病(PD)患者与健康对照组(HC)多个组织和体液中的α-突触核蛋白。S4是一项对患有早、中、晚期PD和HCS的参与者进行的6个部位的横断面观察研究。获得运动和非运动测量和多巴胺转运体SPECT。采集皮肤、结肠、颌下腺(SMG)、脑脊液、唾液和血液的活检标本。组织活检切片用抗病理性α-突触核蛋白的5C12单抗染色；数字图像由盲目诊断的神经病理学家解释。生物体液总α-突触核蛋白定量采用ELISA法。最终队列包括59名帕金森病患者和21名肥胖症患者。帕金森病患者脑脊液α-突触核蛋白低于肥厚型脑脊液，诊断帕金森病的敏感性和特异性分别为87.0%和63.2%。α-突触核蛋白免疫反应诊断帕金森病的敏感性为56.1%，特异性为92.9%，特异性为100%。受试者体内α-突触核蛋白的不同测量之间没有显著的关系。S4证实帕金森病患者脑脊液中总α-突触核蛋白水平低于肥厚性脑病，但特异性较低。相反，α-突触核蛋白在皮肤和SMG中的免疫反应是帕金森病特异的，但敏感性低。参与者之间跨越不同组织和生物体液的关系无法得到证实。迫切需要对α-突触核蛋白的病理形态进行更高精度的检测。本研究提供的III类证据表明，脑脊液总α-突触核蛋白不能准确地区分帕金森病患者和肥厚性脑病患者，而SMG和皮肤总α-突触核蛋白的单抗染色对帕金森病的诊断是特异的，但不敏感。
The Systemic Synuclein Sampling Study (S4) measured α-synuclein in multiple tissues and biofluids within the same patients with Parkinson disease (PD) vs healthy controls (HCs). S4 was a 6-site cross-sectional observational study of participants with early, moderate, or advanced PD and HCs. Motor and nonmotor measures and dopamine transporter SPECT were obtained. Biopsies of skin, colon, submandibular gland (SMG), CSF, saliva, and blood were collected. Tissue biopsy sections were stained with 5C12 monoclonal antibody against pathologic α-synuclein; digital images were interpreted by neuropathologists blinded to diagnosis. Biofluid total α-synuclein was quantified using ELISA. The final cohort included 59 patients with PD and 21 HCs. CSF α-synuclein was lower in patients with PD vs HCs; sensitivity/specificity of CSF α-synuclein for PD diagnosis was 87.0%/63.2%, respectively. Sensitivity of α-synuclein immunoreactivity for PD diagnosis was 56.1% for SMG and 24.1% for skin; specificity was 92.9% and 100%, respectively. There were no significant relationships between different measures of α-synuclein within participants. S4 confirms lower total α-synuclein levels in CSF in patients with PD compared to HCs, but specificity is low. In contrast, α-synuclein immunoreactivity in skin and SMG is specific for PD but sensitivity is low. Relationships within participants across different tissues and biofluids could not be demonstrated. Measures of pathologic forms of α-synuclein with higher accuracy are critically needed. This study provides Class III evidence that total CSF α-synuclein does not accurately distinguish patients with PD from HCs, and that monoclonal antibody staining for SMG and skin total α-synuclein is specific but not sensitive for PD diagnosis.