Parkinson's Disease and Dementia

帕金森病（PD）是仅次于阿尔茨海默病的第二种最常见的神经退行性疾病，影响约1，000，000美国人。PD开始于大约6* 十年，出现运动迟缓、僵硬和静息性震颤。此外，非运动症状发生在PD的任何阶段，并且>80%的PD患者随着疾病进展发展为痴呆（PDD）。认知功能障碍（CI）、执行功能障碍和痴呆增加了PD的负担并增加死亡率，但PD中痴呆的潜在基础尚不清楚，并且没有有效的疾病改善疗法。尽管研究取得了重大进展，但PD/PDD/DLB的确切原因尚不清楚。为了解决这些问题，美国国家神经疾病和中风研究所的Morris K. Udall帕金森病卓越研究中心（Udall Center）于2007年在宾夕法尼亚大学佩雷尔曼医学院（Penn）成立。Penn Udall中心6-10年的竞争性更新建立在其最近的进展基础上，以阐明PD从正常认知到认知障碍（CI）的进展，PDD中的执行功能障碍和痴呆，以及DLB中的疾病进展，以及由病理性α-突触核蛋白（a-syn）的进行性积累介导的中枢神经系统（CNS）变性。因为最近的宾夕法尼亚大学尤德尔中心的研究提出了一个挑衅性的，但非常合理的可能性，即PD/PDD/DLB的进展与病理性a-syn的细胞间传播有关，Penn Udall中心的首要目标是阐明疾病进展的机制，通过基础研究和转化研究项目之间的协同合作进行同步传输，这些项目与每个核心合作，以实现以下使命：宾州尤德尔中心在续约期间。为此，Udall中心更新将实施以下核心和项目：行政核心A：核心Leaer（CL）- J.Q. Trojanowski;临床核心B：CL - H。Hurtig; Co-CL - A Siderowf;神经病理学、生物标志物和遗传学核心C：CL - J.Q. Trojanowski; Co-CL- y。货车Deerlin;合作研究者（Col）- EB.数据管理、生物统计学和生物信息学核心D：CL - S.谢;王立山;项目一：“评估和预测路易体谱系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.格罗斯;项目III：“神经元中病理性α-突触核蛋白的传递机制”：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.