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孤立性快速眼动睡眠行为障碍与帕金森病唾液腺唇下小体双α-突触核蛋白标记与黑质神经黑色素成像的关系。

Relationship between Substantia Nigra Neuromelanin Imaging and Dual Alpha-Synuclein Labeling of Labial Minor in Salivary Glands in Isolated Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease.

机构信息

Centre National de la Recherche Scientifique CNRS, Institut National de la Santé Et de la Recherche Médicale INSERM, Institut du Cerveau ICM, Sorbonne Université, 47-83 Bd de l'Hôpital, 75013 Paris, France.

Clinical Investigation Center for Neurosciences, Department of Neurology, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 47-83 Bd de l'Hôpital, 75013 Paris, France.

出版信息

Genes (Basel). 2022 Sep 24;13(10):1715. doi: 10.3390/genes13101715.

Abstract

We investigated the presence of misfolded alpha-Synuclein (α-Syn) in minor salivary gland biopsies in relation to substantia nigra pars compacta (SNc) damage measured using magnetic resonance imaging in patients with isolated rapid eye movement sleep behavior disorder (iRBD) and Parkinson's disease (PD) as compared to healthy controls. Sixty-one participants (27 PD, 16 iRBD, and 18 controls) underwent a minor salivary gland biopsy and were scanned using a 3 Tesla MRI. Deposits of α-Syn were found in 15 (55.6%) PD, 7 (43.8%) iRBD, and 7 (38.9%) controls using the anti-aggregated α-Syn clone 5G4 antibody and in 4 (14.8%) PD, 3 (18.8%) iRBD and no control using the purified mouse anti-α-Syn clone 42 antibody. The SNc damages obtained using neuromelanin-sensitive imaging did not differ between the participants with versus without α-Syn deposits (irrespective of the antibodies and the disease group). Our study indicated that the α-Syn detection in minor salivary gland biopsies lacks sensitivity and specificity and does not correlate with the SNc damage, suggesting that it cannot be used as a predictive or effective biomarker for PD.

摘要

我们研究了在孤立性快速眼动睡眠行为障碍(iRBD)和帕金森病(PD)患者的小唾液腺活检中是否存在错误折叠的α-突触核蛋白(α-Syn),并与使用磁共振成像测量的黑质致密部(SNc)损伤进行了比较。61 名参与者(27 名 PD、16 名 iRBD 和 18 名对照)接受了小唾液腺活检,并使用 3 Tesla MRI 进行了扫描。使用抗聚集的α-Syn 克隆 5G4 抗体在 15 名(55.6%)PD、7 名(43.8%)iRBD 和 7 名(38.9%)对照中发现了α-Syn 沉积,而使用纯化的小鼠抗-α-Syn 克隆 42 抗体在 4 名(14.8%)PD、3 名(18.8%)iRBD 和无对照中发现了α-Syn 沉积。使用神经黑色素敏感成像获得的 SNc 损伤在有和没有α-Syn 沉积的参与者之间没有差异(无论使用哪种抗体和疾病组)。我们的研究表明,小唾液腺活检中α-Syn 的检测缺乏敏感性和特异性,与 SNc 损伤无关,表明它不能用作 PD 的预测或有效生物标志物。

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