Skin nerve misfolded -synuclein in pure autonomic failure and Parkinson disease
Skin nerve misfolded -synuclein in pure autonomic failure and Parkinson disease
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DOI：
10.1002/ana.24567
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发表时间：
2016-02-01
影响因子：
11.2
通讯作者：
Liguori, Rocco
中科院分区：
文献类型：
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作者：
Donadio, Vincenzo;Incensi, Alex;Liguori, Rocco
目的表征纯自主神经衰竭（PAF）和特发性帕金森病（IPD）中天然（n-syn）和错误折叠磷酸化（p-syn）突触核蛋白在皮肤神经中的表达。具体目标是 (1) 定义 n-syn 和 p-syn 作为疾病生物标志物的重要性，以及 (2) 确定异常突触核蛋白皮肤神经沉积物的差异。方法我们研究了 30 名患者，包括 16 名特征明确的 IPD 患者和 14 名符合 PAF 诊断标准的患者，以及 15 名年龄匹配的对照者。受试者从近端（即颈部）和远端（即大腿和小腿）部位进行皮肤活检，以研究小神经纤维和神经内 n-syn 和 p-syn。 结果 PAF 和 IPD 显示长度依赖性躯体和自主小纤维丢失，在 p-syn 负荷较高的患者中表达更严重。 n-syn 在两组患者和对照组中表达相似。相比之下，p-syn 在对照组的任何皮肤样本中均不明显，但在所有 PAF 和 IPD 患者中均发现，尽管其皮肤神经支配不同。此外，在所有分析的PAF皮肤样本中均发现了异常的β-突触核蛋白沉积，但在IPD近端部位阳性率较高的样本中，仅49%的样本中发现了异常的β-突触核蛋白沉积。解释(1)神经内p-syn是PAF和IPD的可靠体内标志物； (2) PAF 和 IPD 中的神经炎 p-syn 内含物不同，表明潜在的发病机制不同； (3) 当寻找皮肤神经中异常的 p-syn 沉积物时，分析部位在 PAF 中无关紧要，但在 IPD 中至关重要。安·尼罗尔 2015 年 安·尼罗尔 2016；79:306-316
ObjectiveTo characterize the expression in skin nerves of native (n-syn) and misfolded phosphorylated (p-syn) -synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). The specific aims were to (1) define the importance of n-syn and p-syn as disease biomarkers and (2) ascertain differences in abnormal synuclein skin nerve deposits.MethodsWe studied 30 patients, including 16 well-characterized IPD patients and 14 patients fulfilling PAF diagnostic criteria, and 15 age-matched controls. Subjects underwent skin biopsy from proximal (ie, cervical) and distal (ie, thigh and leg) sites to study small nerve fiber and intraneural n-syn and p-syn.ResultsPAF and IPD showed length-dependent somatic and autonomic small fiber loss, more severely expressed in patients with higher p-syn load. n-syn was similarly expressed in both groups of patients and controls. By contrast, p-syn was not evident in any skin sample of controls but was found in all PAF and IPD patients, although with different skin innervation. In addition, abnormal -synuclein deposits were found in all analyzed skin samples in PAF but in only 49% of samples with a higher positivity rate at the proximal site in IPD.Interpretation(1) Intraneural p-syn was a reliable in vivo marker of PAF and IPD; (2) neuritic p-syn inclusions differed in PAF and IPD, suggesting a different underlying pathogenesis; (3) when searching for abnormal p-syn deposits in skin nerves, the site of analysis is irrelevant in PAF but it is critical in IPD. Ann Neurol 2015 Ann Neurol 2016;79:306-316