Cutaneous neuropathy in Parkinson's disease: a window into brain pathology.
Cutaneous neuropathy in Parkinson's disease: a window into brain pathology.
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DOI：
10.1007/s00401-014-1284-0
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发表时间：
2014-07
影响因子：
12.7
通讯作者：
Sommer C
中科院分区：
文献类型：
--
作者：
Doppler K;Ebert S;Uçeyler N;Trenkwalder C;Ebentheuer J;Volkmann J;Sommer C
α-突触核蛋白在脑中的沉积是帕金森病（PD）的神经病理学标志，其遵循独特的解剖学和时间序列。本研究旨在表征PD患者皮神经中的α-突触核蛋白沉积。我们进一步努力探索周围神经受累是否是PD固有的，并反映已知的脑病理学特征，这可能使其成为PD发病机制研究和尸检组织学诊断的有用工具。我们从31名PD患者和35名对照的远端和近端腿部、背部和手指获得皮肤活检，并量化了躯体感觉和自主神经纤维中磷酸化α-突触核蛋白的共定位以及不同亚型真皮纤维的丢失模式。在16/31名PD患者中鉴定出磷酸化α-突触核蛋白的沉积物，但在0/35名对照中鉴定出磷酸化α-突触核蛋白的沉积物（p < 0.0001）。神经纤维的定量显示PD中有两种类型的周围神经变性：（1）表皮内小神经纤维的长度依赖性减少（p < 0.05）和（2）P物质免疫反应性表皮内神经纤维的严重非长度依赖性减少（p < 0.0001）。后者与皮肤中α-突触核蛋白病理学的更明显的近端表现相吻合。组织学变化与左旋多巴毒性标志物（如维生素B12缺乏）无关。我们的研究结果表明，周围神经纤维的损失是PD的内在特征，周围神经的变化可能反映了两种类型的中枢α-突触核蛋白相关的PD病理，即神经元死亡和轴突变性。检测真皮神经纤维中磷酸化的α-突触核蛋白可能是一种有用的诊断PD的测试，具有高特异性，但敏感性低。本文的在线版本（doi：10.1007/s 00401 -014-1284-0）包含补充材料，可供授权用户使用。
The deposition of alpha-synuclein in the brain, the neuropathological hallmark of Parkinson’s disease (PD), follows a distinct anatomical and temporal sequence. This study aimed to characterize alpha-synuclein deposition in cutaneous nerves from patients with PD. We further strived to explore whether peripheral nerve involvement is intrinsic to PD and reflective of known features of brain pathology, which could render it a useful tool for pathogenetic studies and pre-mortem histological diagnosis of PD. We obtained skin biopsies from the distal and proximal leg, back and finger of 31 PD patients and 35 controls and quantified the colocalization of phosphorylated alpha-synuclein in somatosensory and autonomic nerve fibers and the pattern of loss of different subtypes of dermal fibers. Deposits of phosphorylated alpha-synuclein were identified in 16/31 PD patients but in 0/35 controls (p < 0.0001). Quantification of nerve fibers revealed two types of peripheral neurodegeneration in PD: (1) a length-dependent reduction of intraepidermal small nerve fibers (p < 0.05) and (2) a severe non-length-dependent reduction of substance P-immunoreactive intraepidermal nerve fibers (p < 0.0001). The latter coincided with a more pronounced proximal manifestation of alpha-synuclein pathology in the skin. The histological changes did not correlate with markers of levodopa toxicity such as vitamin B12 deficiency. Our findings suggest that loss of peripheral nerve fibers is an intrinsic feature of PD and that peripheral nerve changes may reflect the two types of central alpha-synuclein-related PD pathology, namely neuronal death and axonal degeneration. Detection of phosphorylated alpha-synuclein in dermal nerve fibers might be a useful diagnostic test for PD with high specificity but low sensitivity. The online version of this article (doi:10.1007/s00401-014-1284-0) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Lebouvier T;Neunlist M;Bruley des Varannes S;Coron E;Drouard A;N'Guyen JM;Chaumette T;Tasselli M;Paillusson S;Flamand M;Galmiche JP;Damier P;Derkinderen P
通讯作者：
Derkinderen P
影响因子：
14.5
作者：
GAI, WP;HALLIDAY, GM;BLESSING, WW
通讯作者：
BLESSING, WW
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
11.2
作者：
HALLIDAY, GM;LI, YW;GEFFEN, LB
通讯作者：
GEFFEN, LB
影响因子：
14.5
作者：
Fernandez, A;deCeballos, ML;Marsden, CD
通讯作者：
Marsden, CD