CORE A: Administrative Core

项目/核心：行政核心A 项目/核心负责人姓名：John Q. Trojanowski，医学博士，哲学博士 项目概要/摘要 核心A是U19“α-突触核蛋白中心”重新提交申请的管理核心 阿尔茨海默病和相关痴呆症的菌株”，宾夕法尼亚大学（Penn）Perelman 医学院（PSOM）。它有助于实现这一多学科研究计划的目标， 阐明由不同病理性α- 突触核蛋白（aSyn）是阿尔茨海默病（AD）和相关痴呆中认知障碍的基础， ADRD，包括路易体（LB）疾病（LBD），如痴呆伴LB（DLB）和帕金森病 无痴呆（PD）或有痴呆（PDD）。在ADRD中，AD与丰富的LB共病最为常见 AD亚型。因此，AD与aSyn LB（AD+LB）、PDD和DLB一起代表最常见的形式 与衰老有关的痴呆症因此，这个新的宾夕法尼亚州AD和LBD U19中心的总体目标是阐明 AD+LB相对于纯AD（AD-LB）中病理性aSyn介导的进行性神经变性的机制 与LBD作为老化的函数以及aSyn、tau和Aβ的异质性积累相比， 影响这些疾病的不同临床表现的病理学。我们假设 病理性aSyn的积累导致神经元功能障碍和由于错误折叠和传递而死亡 不同的病理性aSyn菌株形成LB和LN的能力，与那些潜在的aSyn菌株相比， 多系统萎缩（MSA），特征为自MSA aSyn菌株以来的神经胶质细胞质包涵体（GCI） 很少引起共病AD病理，并且痴呆很少发生在MSA患者中。具体来说，我们追求 跨中心的共同目标是将项目III/IV的深层表型数据与菌株数据直接关联起来 在项目I/II中与核心小组合作，首次确定 我们的初步数据总结了新型aSyn菌株的临床病理表型， 项目（另见“总体组成部分”中的图1和图2）。为了实现其目标，核心A将实现 以下目标：监督该U19中心的预算和财务方面，并指导 核心和项目;促进/促进核心和项目之间的互动，以及宾夕法尼亚大学的互动 U19研究人员与宾夕法尼亚大学U19中心以外的科学家在宾夕法尼亚大学及以外;作为一个信息 为患者社区和公众提供关于LBD和MSA的资源;促进数据共享， U19中心与NIA合作的其他研究人员产生的试剂和资源;培训 下一代AD/LBD研究者这样，核心A在宾夕法尼亚大学U19中心发挥着关键作用， 促进其使命的完成。

PROJECT/CORE: Administrative Core A Project/Core Leader Name: John Q. Trojanowski, MD, PhD Project Summary/Abstract Core A is the Administrative Core of this re-submitted application for a U19 “Center On Alpha-synuclein Strains In Alzheimer Disease & Related Dementias” at the University of Pennsylvania (Penn) Perelman School of Medicine (PSOM). It facilitates accomplishing the goals of this multidisciplinary research program to elucidate mechanisms of progressive neurodegeneration mediated by different strains of pathological alpha- synuclein (aSyn) underlying cognitive impairments in Alzheimer's disease (AD) and related dementias or ADRD including Lewy body (LB) diseases (LBD) such as dementia with LBs (DLB) and Parkinson's disease without (PD) or with dementia (PDD). Among ADRD, AD with abundant LB co-pathology is the most common subtype of AD. Hence, AD with aSyn LB (AD+LB), PDD and DLB together represent the most common forms of aging related dementias. Thus, the overall goals of this new Penn AD and LBD U19 Center are to elucidate mechanisms of pathological aSyn mediated progressive neurodegeneration in AD+LB versus pure AD (AD-LB) compared with LBD as a function of aging and the heterogeneous accumulations of aSyn, tau and Aβ pathologies that influence different clinical manifestations of these disorders. We hypothesize that accumulations of pathological aSyn lead to neuron dysfunction and death due to misfolding and transmission of different strains of pathological aSyn to form LBs and LNs compared to those aSyn strains underlying multiple system atrophy (MSA) characterized by glial cytoplasmic inclusions (GCI) since the MSA aSyn strain rarely induces comorbid AD pathology and dementia rarely occurs in MSA patients. Specifically, we pursue the cross-Center shared goal to correlate deep phenotypic data from Projects III/IV directly with strain data generated in Projects I/II in collaboration with the Cores to determine for the first time the correspondence of clinicopathological phenotypes with the novel aSyn strains defined by our preliminary data summarized in each Project (see also Fig. 1 and 2 in the “Overall Component”). To accomplish its goals, Core A will implement the following Aims: oversee budgetary and fiscal aspects of this U19 Center and guide the progress of the Cores and Projects; promote/foster interactions between Cores and Projects, as well as interactions of Penn U19 investigators with scientists outside the Penn U19 Center at and beyond Penn; serve as an information resource for the patient community and general public regarding LBD and MSA; facilitate the sharing of data, reagents, and resources generated by the U19 Center with other researchers in partnership with the NIA; train the next generation of AD/LBD investigators. In this manner, Core A plays a key role in the Penn U19 Center to foster accomplishment of its mission.