Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA.
Mov Disord. 2011 Jul;26(8):1436-42. doi: 10.1002/mds.23697. Epub 2011 May 3.
The ability to understand how Parkinson's disease neurodegeneration leads to cortical dysfunction will be critical for developing therapeutic advances in Parkinson's disease dementia. The overall purpose of this project was to study the small-amplitude cortical myoclonus in Parkinson's disease as an in vivo model of focal cortical dysfunction secondary to Parkinson's disease neurodegeneration. The objectives were to test the hypothesis that cortical myoclonus in Parkinson's disease is linked to abnormal levels of α-synuclein in the primary motor cortex and to define its relationship to various biochemical, clinical, and pathological measures. The primary motor cortex was evaluated for 11 Parkinson's disease subjects with and 8 without electrophysiologically confirmed cortical myoclonus (the Parkinson's disease + myoclonus group and the Parkinson's disease group, respectively) who had premortem movement and cognitive testing. Similarly assessed 9 controls were used for comparison. Measurements for α-synuclein, Aβ-42 peptide, and other biochemical measures were made in the primary motor cortex. A 36% increase in α-synuclein was found in the motor cortex of Parkinson's disease + myoclonus cases when compared with Parkinson's disease without myoclonus. This occurred without significant differences in insoluble α-synuclein, phosphorylated to total α-synuclein ratio, or Aβ-42 peptide levels. Higher total motor cortex α-synuclein levels significantly correlated with the presence of cortical myoclonus but did not correlate with multiple clinical or pathological findings. These results suggest an association between elevated α-synuclein and the dysfunctional physiology arising from the motor cortex in Parkinson's disease + myoclonus cases. Alzheimer's disease pathology was not associated with cortical myoclonus in Parkinson's disease. Cortical myoclonus arising from the motor cortex is a model to study cortical dysfunction in Parkinson's disease.
帕金森病神经退行性变导致皮质功能障碍的能力对于开发帕金森病痴呆症的治疗进展至关重要。本项目的总体目的是研究帕金森病中的小幅度皮质肌阵挛，作为帕金森病神经退行性变引起的局灶性皮质功能障碍的体内模型。目的是检验以下假设：帕金森病中的皮质肌阵挛与初级运动皮层中α-突触核蛋白的异常水平有关，并定义其与各种生化、临床和病理测量的关系。评估了 11 名帕金森病患者（有和没有电生理证实的皮质肌阵挛）的初级运动皮层，其中 8 名帕金森病患者（有和没有电生理证实的皮质肌阵挛）（帕金森病+肌阵挛组和帕金森病组）在生前进行了运动和认知测试。同样评估了 9 名对照用于比较。在初级运动皮层测量了α-突触核蛋白、Aβ-42 肽和其他生化指标。与帕金森病无肌阵挛组相比，帕金森病+肌阵挛组的运动皮层中α-突触核蛋白增加了 36%。这并没有导致不溶性α-突触核蛋白、磷酸化α-突触核蛋白与总α-突触核蛋白的比值或 Aβ-42 肽水平的显著差异。总运动皮层α-突触核蛋白水平升高与皮质肌阵挛的存在显著相关，但与多个临床或病理发现无关。这些结果表明，在帕金森病+肌阵挛组中，α-突触核蛋白升高与运动皮层的功能障碍生理之间存在关联。阿尔茨海默病病理学与帕金森病中的皮质肌阵挛无关。源自运动皮层的皮质肌阵挛是研究帕金森病皮质功能障碍的模型。
