CORE A: Administrative Core

核心 A:行政核心

基本信息

  • 批准号:
    10373916
  • 负责人:
  • 金额:
    $ 45.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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,博士 项目摘要/摘要 核心A是重新提交的U19“阿尔法-突触核蛋白中心”申请的行政核心 宾夕法尼亚大学佩雷尔曼分校的《阿尔茨海默病和相关痴呆症的菌株》 医学院(PSOM)。它有助于实现这一多学科研究计划的目标 阐明不同菌株病理性α-受体介导的进行性神经退行性变的机制 阿尔茨海默病(AD)及相关痴呆患者认知损害的突触核蛋白(ASyn) ADRD包括路易体(LBD)病(LBD),如伴有LBS的痴呆症(DLB)和帕金森氏病 无痴呆(PD)或痴呆(PDD)。在ADRD中,伴有丰富的Lb共病的AD最为常见 AD的亚型。因此,带有Syn Lb(AD+Lb)的AD、PDD和DLb一起表示最常见的形式 与衰老相关的痴呆症。因此,这个新的宾夕法尼亚AD和LBD U19中心的总体目标是阐明 病理性aSyn介导AD+LB型与单纯AD(AD-LB型)进行性神经变性的机制 与LBD相比,随着年龄的增长和aSyn、tau和Aβ的非均相积累 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错误折叠和传递导致的死亡 形成LBS和LNS的不同病理性aSyn菌株与基础aSyn菌株的比较 多系统萎缩(MSA)aSyn株以来以胶质细胞质内含物(GCI)为特征的MSA 在MSA患者中很少引起AD的共病病理,痴呆也很少发生。具体地说,我们追求 跨中心共同目标,将项目III/IV的深层表型数据直接与菌株数据相关联 在项目一/二中与核心协作产生的,以首次确定 由我们的初步数据定义的新型aSyn菌株的临床病理表型 项目(另见“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U19中心的预算和财政方面,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调查人员和宾夕法尼亚大学U19中心外的科学家;作为信息 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合作产生的试剂和资源;培训 下一代AD/LBD调查员。通过这种方式,核心A在宾夕法尼亚大学U19中心扮演着关键角色 促进其使命的完成。

项目成果

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JOHN Q. TROJANOWSKI其他文献

JOHN Q. TROJANOWSKI的其他文献

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{{ truncateString('JOHN Q. TROJANOWSKI', 18)}}的其他基金

CORE A: Administrative Core
核心 A:行政核心
  • 批准号:
    10654793
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
Neuropathology, Biomarker & Genetics Core C
神经病理学,生物标志物
  • 批准号:
    10452560
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
CORE A: Administrative Core
核心 A:行政核心
  • 批准号:
    10452558
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
Neuropathology, Biomarker & Genetics Core C
神经病理学,生物标志物
  • 批准号:
    10654796
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
Neuropathology, Biomarker & Genetics Core C
神经病理学,生物标志物
  • 批准号:
    10373918
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
CORE A: Administrative Core
核心 A:行政核心
  • 批准号:
    10020330
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
Neuropathology, Biomarker & Genetics Core C
神经病理学,生物标志物
  • 批准号:
    10020332
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
Project II "aSyn Strains & Diverse Synucleinopathies"
项目二“aSyn菌株
  • 批准号:
    10020335
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
Project II "aSyn Strains & Diverse Synucleinopathies"
项目二“aSyn菌株
  • 批准号:
    10452563
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:
Project II "aSyn Strains & Diverse Synucleinopathies"
项目二“aSyn菌株
  • 批准号:
    10654805
  • 财政年份:
    2019
  • 资助金额:
    $ 45.27万
  • 项目类别:

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