Parkinson's Disease and Dementia

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） Morris K. Udall帕金森病卓越研究中心（Udall中心）提出的这项新申请，建立在宾夕法尼亚大学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）研究项目的总体目标。简而言之，Udall中心的目标是阐明PD患者脑变性的机制，特别是那些鲜为人知的潜在神经精神损伤。PD伴痴呆（PD with dementia， PDD）在病理和临床上可能与路易体痴呆（dementia with Lewy bodies， DLB）难以区分，常与阿尔茨海默病（Alzheimer's disease， AD）共发，而AD的路易体变异体是AD最常见的亚型。然而，ibbs和AD病理趋同的原因仍然是个谜。在这里，我们假设a-突触核蛋白低聚物/原纤维物种的积累导致神经变性和神经精神障碍，除了帕金森症，这可能与α -突触核蛋白低聚物/原纤维介导的tau和β病理相结合。为了实现宾夕法尼亚大学尤德尔中心的目标，项目1和项目2是面向患者的研究，旨在开发：1)疾病特异性评分量表，评估认知障碍对PDD患者日常功能的影响；2)功能影像学研究，以更好地确定PD和PDD中认知障碍的解剖学基础。项目3和4将以患者为导向的研究与新型PD/PDD动物模型的研究联系起来，以阐明a-synuclein、tau和Abeta的错误折叠、纤维化和聚集如何导致PDD患者的神经元功能障碍和变性，从而导致认知障碍。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核心(C)和数据管理和生物统计学核心(D)提供支持。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以及与其他尤德尔中心的合作来实现上述目标。此外，宾夕法尼亚大学尤德尔中心产生的数据、试剂和资源将与其他尤德尔中心的研究人员共享。因此，宾大尤德尔中心团队将有助于改善PD、PDD、DLB及相关疾病患者的诊断和管理。

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.