Parkinson's Disease and Dementia

帕金森病和痴呆症

• 批准号: 7442312
• 负责人: JOHN Q. TROJANOWSKI
• 金额: $ 189.16万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7442312
• 关键词: Parkinson; Disease; Dementia

DESCRIPTION (provided by applicant): This new application from the University of Pennsylvania School of Medicine (PENN) for a National Institute of Neurological Disorders and Stroke (NINDS) Morris K. Udall Parkinson's Disease Research Center of Excellence (Udall Center) builds on the continuing momentum of a team of PENN clinical and basic scientists to accomplish the overarching goals of this new multidisciplinary Parkinson's disease (PD) research program. Briefly, the goals of this Udall Center are to elucidate mechanisms of brain degeneration in patients with PD, especially those underlying poorly understood neuropsychiatric impairments. PD with dementia (PDD), which may be pathologically and clinically indistinguishable from dementia with Lewy bodies (DLB) frequently co-occurs with Alzheimer's disease (AD), and the Lewy body (LB) variant of AD is the most common subtype of AD. However, the reasons for the convergence of IBs and AD pathologies remain enigmatic. Here, we hypothesize that accumulations of oligomeric/fibrillar species of a-synuclein lead to neurodegeneration and neuropsychiatric deficits in addition to parkinsonism, which may be compounded by tau and Abeta pathologies seeded by alpha-synuclein oligomers/fibrils. To accomplish the goals of the PENN Udall Center, Projects 1 and 2 are patient-oriented studies designed to develop: 1) a disease-specific rating scale to assess the impact of cognitive impairment on daily function in PDD; and 2) a functional imaging study to better define the anatomic substrate of cognitive impairment in PD and PDD. Projects 3 and 4 bridge patient oriented studies and research on novel animal models of PD/PDD to clarify how the misfolding, fibrillization and aggregation of a-synuclein, tau and Abeta contribute to the neuron dysfunction and degeneration that result in cognitive impairments in PDD. These 4 highly integrated and synergistic Projects are supported by an Administrative Core (A), a Clinical and Education Core (B), a Neuropathology and Genetics (C) and a Data Management and Biostatistics Core (D). The PENN Udall Center investigators will accomplish the goals outlined above by working in a seamlessly interdisciplinary manner as well as by collaborating with other Udall Centers. Further, data, reagents, and resources generated by the PENN Udall Center will be shared with researchers at other Udall Centers. Thus, the PENN Udall Center team will contribute to improving the diagnosis and management of patients with PD, PDD, DLB and related disorders.

描述（由申请人提供）： 宾夕法尼亚大学医学院（PENN）的这一新应用是国家神经系统疾病与中风研究所（NINDS）Morris K. Udall Parkinson疾病研究中心（UDALL CENTER）（UDALL CENTER）建立在宾夕法尼亚州临床和基础科学家的持续势头的基础上，以实现这一新的多个公园派对（PAR）的统一范围。简而言之，这个UDALL中心的目标是阐明PD患者的脑变性机制，尤其是那些基本知识较差的神经精神障碍的人。痴呆症（PDD）的PD在病理和临床上与痴呆症与Lewy Bodies（DLB）经常与阿尔茨海默氏病（AD）共生，而AD的Lewy体（LB）变体是最常见的广告亚类型。但是，IBS和AD病理的融合的原因仍然是神秘的。在这里，我们假设A-突触核蛋白的低聚/原纤维物种的积累导致神经退行性和神经精神上的缺陷，除帕金森主义外，tau和Abeta病理学还可以由Alpha-synuclein dolegomers/fibirils播种。为了实现Penn Udall中心的目标，项目1和2是旨在发展的患者研究的研究：1）评估认知障碍对PDD日常功能的影响； 2）一项功能成像研究，以更好地定义PD和PDD认知障碍的解剖底物。项目3和4桥式患者面向患者的研究以及对PD/PDD新型动物模型的研究，以阐明A-突触核蛋白，TAU和ABETA的错误折叠，纤颤和聚集如何导致神经元功能障碍以及变性，从而导致PDD认知障碍。这4个高度整合和协同的项目得到了行政核心（a），临床和教育核心（B），神经病理学和遗传学（C）以及数据管理和生物统计学核心（D）的支持。 Penn Udall中心调查人员将通过以无缝的跨学科方式以及与其他Udall中心合作来实现上述目标。此外，Penn Udall中心生成的数据，试剂和资源将与其他Udall中心的研究人员共享。因此，Penn Udall中心团队将有助于改善PD，PDD，DLB和相关疾病患者的诊断和管理。