Parkinson's Disease and Dementia

描述（由申请人提供）： 宾夕法尼亚大学医学院（PENN）为国家神经疾病和中风研究所（NINDS）的莫里斯·K·卡耐基（Morris K. Udall帕金森病卓越研究中心（Udall中心）建立在宾夕法尼亚州临床和基础科学家团队的持续动力基础上，以实现这一新的多学科帕金森病（PD）研究计划的总体目标。简而言之，Udall中心的目标是阐明PD患者脑变性的机制，特别是那些对神经精神损害知之甚少的患者。PD伴痴呆（PDD）在病理学和临床上可能与路易体痴呆（DLB）难以区分，其经常与阿尔茨海默病（AD）共同发生，并且AD的路易体（LB）变体是AD的最常见亚型。然而，IB和AD病理学的融合的原因仍然是谜。在这里，我们假设α-突触核蛋白的寡聚物/纤维状物质的积累除了帕金森症之外还导致神经变性和神经精神缺陷，这可能由α-突触核蛋白寡聚物/纤维接种的tau和Abeta病理复合。为了实现PENN Udall中心的目标，项目1和2是以患者为导向的研究，旨在开发：1）疾病特异性评级量表，以评估认知障碍对PDD日常功能的影响; 2）功能成像研究，以更好地定义PD和PDD认知障碍的解剖学基础。项目3和项目4是以患者为导向的研究和PD/PDD新型动物模型研究的桥梁，旨在阐明α-突触核蛋白、tau和Abeta的错误折叠、纤维化和聚集如何导致神经元功能障碍和变性，从而导致PDD的认知障碍。这4个高度整合和协同的项目由行政核心（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）支持。宾夕法尼亚大学尤德尔中心的研究人员将通过无缝跨学科的方式工作以及与其他尤德尔中心合作来实现上述目标。此外，数据，试剂，并由宾夕法尼亚大学尤德尔中心产生的资源将与其他尤德尔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。

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.