CORE A: Administrative Core

核心 A：行政核心

• 批准号: 10373916
• 负责人: JOHN Q. TROJANOWSKI
• 金额: $ 45.27万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373916
• 关键词: Address; Administrator; Advisory Committees; Aging; Alzheimer' s Disease; Alzheimer' s Disease Core Center; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease therapy; Amyloid beta-Protein; Biological; Cells; Cessation of life; Clinical; Clinical Trials; Clinical and Translational Science Awards; Collaborations; Communities; Cytoplasmic Inclusion; Data; Dementia; Dementia with Lewy Bodies; Disease; Doctor of Philosophy; Education; Ensure; Event; Fostering; Foundations; Foxes; Functional disorder; Funding; General Population; Goals; Heterogeneity; Impaired cognition; Individual; Information Resources; Institutes; Interdisciplinary Study; Lead; Lewy Bodies; Lewy Body Disease; Lewy body pathology; Life; Mediating; Medical center; Mentors; Mission; Monitor; Movement Disorders; Multiple System Atrophy; Names; National Institute of Neurological Disorders and Stroke; Neurodegenerative Disorders; Neurologic; Neurons; Parkinson Disease; Parkinson' s Dementia; Parkinsonian Disorders; Pathologic; Pathology; Patients; Pennsylvania; Phenotype; Philadelphia; Play; Policies; Privatization; Reagent; Research; Research Personnel; Resource Sharing; Resources; Sampling; Science; Scientist; Therapeutic; Time; Training; United States Department of Veterans Affairs; United States National Institutes of Health; Universities; Work; Yang; alpha synuclein; austin; career; clinical center; common symptom; comorbidity; cost; data resource; data sharing; human subject; medical schools; meetings; mortality; neuroimaging; next generation; non-motor symptom; novel; outreach; phenotypic data; programs; progression marker; progressive neurodegeneration; social media; synucleinopathy; tau Proteins; translational medicine; translational neuroscience; transmission process; web site

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.

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 是此重新提交的 U19“α-突触核蛋白中心”申请的管理核心 宾夕法尼亚大学 (Penn) Perelman 的《阿尔茨海默病及相关痴呆症菌株》 医学院（PSOM）有助于实现这一多学科研究计划的目标 阐明不同病理性α-菌株介导的进行性神经变性的机制 突触核蛋白 (aSyn) 是阿尔茨海默氏病 (AD) 和相关痴呆症中潜在的认知障碍或 ADRD 包括路易体 (LB) 疾病 (LBD)，例如 LB 痴呆 (DLB) 和帕金森病 不伴有痴呆 (PD) 或伴有痴呆 (PDD) 的 ADRD 中，伴有大量 LB 共同病理的 AD 是最常见的。 因此，AD 与 aSyn LB (AD+LB)、PDD 和 DLB 一起代表了最常见的形式。 因此，这个新的 Penn AD 和 LBD U19 中心的总体目标是阐明与衰老相关的痴呆症。 AD+LB 与纯 AD (AD-LB) 中病理性 aSyn 介导的进行性神经变性的机制 与 LBD 相比，作为衰老的函数以及 aSyn、tau 和 Aβ 的异质积累 影响这些疾病不同临床表现的病理学。 病理性 aSyn 的积累会因错误折叠和传递而导致神经元功能障碍和死亡 与潜在的 aSyn 菌株相比，不同菌株的病理性 aSyn 形成 LB 和 LN 自 MSA aSyn 菌株以来，以神经胶质细胞质内含物 (GCI) 为特征的多系统萎缩 (MSA) MSA 患者很少诱发 AD 病理，并且很少发生痴呆。具体来说，我们追求的是： 跨中心的共同目标是将项目 III/IV 的深层表型数据直接与菌株数据相关联 与核心合作在项目 I/II 中生成，首次确定 由我们在每个中总结的初步数据定义的新型 aSyn 菌株的临床病理表型 项目（另请参见“总体组件”中的图 1 和图 2） 为了实现其目标，核心 A 将实施。 以下目标：监督该 U19 中心的预算和财务方面并指导该中心的进展 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 调查人员与宾夕法尼亚大学 U19 中心内外的科学家一起提供信息； 为患者社区和公众提供有关 LBD 和 MSA 的资源，促进数据共享； U19 中心与其他研究人员与 NIA 合作开发的试剂和资源； 通过这种方式，Core A 在 Penn U19 中心发挥着关键作用。 促进其使命的完成。