Parkinson's Disease and Dementia

帕金森氏病(PD)是仅次于阿尔茨海默病的第二大常见神经退行性疾病，影响着100万美国人。帕金森病始于大约6*10年，开始出现运动迟缓、僵硬和静止性震颤。此外，非运动症状出现在帕金森病的任何阶段，80%的帕金森病患者会随着疾病的进展而患上痴呆症(PDD)。认知功能障碍(CI)、执行功能障碍和痴呆增加了PD的负担，增加了死亡率，但PD痴呆的潜在基础尚不清楚，也没有有效的疾病调整治疗方法。尽管取得了重大的研究进展，但PD/PDD/DLB的确切原因尚不清楚。为了解决这些问题，2007年在宾夕法尼亚大学佩雷尔曼医学院(Penn)成立了国家神经疾病和中风莫里斯·K·尤德尔帕金森病卓越研究中心(尤德尔中心)。宾夕法尼亚大学Udall中心6-10年的竞争性更新建立在其最新进展的基础上，以阐明PD从正常认知到认知损害(CI)、PDD中的执行功能障碍和痴呆的进展，以及DLB中的疾病进展，以及由病理性α-突触核蛋白(a-syn)逐渐积累所介导的中枢神经系统(CNS)退化。由于宾夕法尼亚大学Udall中心最近的研究提出了一种具有挑衅性但极具说服力的可能性，即PD/PDD/DLB的进展与病理性a-syn的细胞间传播有关，因此宾夕法尼亚大学Udall中心的首要目标是通过基础研究项目和翻译研究项目之间的协同合作来阐明疾病进展和a-syn传播的机制，这些项目与每个核心一起工作，以实现宾夕法尼亚大学Udall中心在更新期的使命。为此，尤德尔中心的更新将实施以下核心和项目：行政核心A：核心离职(CL)-J.Q.Trojanowski；临床核心B：CL-H.Hurtig；Co-CL-A Siderowf；神经病理学、生物标记和遗传学核心C：CL-J.Q.Trojanowski；Co-CL-Y.van Deerlin；联合调查员(COL)-EB。数据管理、生物统计和生物信息学核心D：CL-S.Xie；Co-i-Li-San Wang；项目I：“评估和预测路易体谱障碍认知功能下降的多模式生物标志物方法”：项目负责人(PL)-A.Siderowf；Co-I-A.Chen-Plotkin；项目II：“语言中PD执行功能障碍的机制”：PL-M.Grossman；Co-I-R.Gross；项目III：“病理性α-突触核蛋白在神经元中的传递机制”：Pl-V.M.-Y.Lee；项目IV：“免疫疗法阻止帕金森病在小鼠中的传播”：PL-J.Q.Trojanowski；Co-i-V.M.-Y.Lee和Kelvin Luk。

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease affecting -1,000,000 Americans. PD begins about the 6* decade with onset of bradykinesia, rigidity, and resting tremor. In addition, non-motor symptoms occur at any stage of PD, and >80% of PD patients develop dementia (PDD) with disease progression. Cognitive impairment (CI), executive dysfunction and dementia add to the burden of PD and increase mortality, but the underlying basis of dementia in PD is unclear, and there are no effective disease modifying therapies. Despite significant research advances, the exact causes of PD/PDD/DLB are unknown. To address these issues, a National Institute of Neurological Disorders and Stroke Morris K. Udall Parkinson's Disease Research Center of Excellence (Udall Center) was launched at the Perelman School of Medicine (Penn) of the University of Pennsylvania in 2007. The competing renewal for years 6-10 of the Penn Udall Center builds on its recent progress to elucidate the progression of PD from normal cognition to cognitive impairment (CI), executive dysfunction and dementia in PDD, as well as disease progression in DLB in addition to the central nervous system (CNS) degeneration mediated by progressive accumulations of pathological alpha-synuclein (a-syn). Because recent Penn Udall Center studies raise the provocative, but highly plausible possibility that the progression of PD/PDD/DLB is linked to the cell-to-cell spread of pathological a-syn, the overarching goals of the Penn Udall Center are to elucidate mechanisms of disease progression and a-syn transmission through synergistic collaborations between basic and translational research Projects that work with each of the Cores to implement the mission of the Penn Udall Center in the renewal period. To that end, the Udall Center renewal will implement the following Cores and Projects: Administrative Core A: Core Leaer (CL) - J.Q. Trojanowski; Clinical Core B: CL - H. Hurtig; Co-CL - A Siderowf; Neuropathology, Biomarker and Genetics Core C: CL - J.Q. Trojanowski; Co- CL - y. Van Deerlin; Co-Investigator (Col) - EB. Lee; Data Management, Biostatistics and Bioinformatics Core D: CL - S. Xie; Co-I - Li-San Wang; Project I: "A Multimodal Biomarker Approach to Evaluating and Predicting Cognitive Decline in Lewy Body Spectrum Disorders": Project Leader (PL) - A. Siderowf; Co-I - A. Chen-Plotkin; Project II: "Mechanisms Of PD Executive Dysfunction In Language": PL - M. Grossman; Co-I - R. Gross; Project III: "Mechanisms Of Transmission Of Pathological Alpha-synuclein In Neurons": PL - V.M.-Y. Lee; Project IV: "Immune Therapy To Block PD Transmission In Mice": PL - J.Q. Trojanowski; Co-I - V.M.-Y. Lee and Kelvin Luk.