Administrative Core

额颞部退行性变(FTD)是一种临床上未被充分研究的神经退行性疾病。尽管如此，这 是65岁以下人群中仅次于阿尔茨海默病(AD)的最常见的痴呆症。最常见的 与FTD痴呆相关的病理是过敏性额颞叶变性(FTLD) ~43kD的DNA结合蛋白(TDP-43)，称为FTLD-TDP。在ALS和ALS中也发现FTLD-TDP病理 许多其他与衰老相关的疾病，包括以边缘为主的年龄相关的TDP-43 脑病(晚期)。自从我们在人类疾病中发现FTLD-TDP以来，在理解 人类FTLD-TDP病理的病理生理和传播与患者生前辨别能力差 由于TDP-43的病理导致的痴呆症一直是发展疾病修改的巨大障碍 针对这种病理的治疗方法。在本计划项目拨款(PPG)中，我们提出了一种新颖的和 独特的多学科研究计划，专注于阐明人类的病理生理机制 TDP-43病理，鉴定FTLD-TDP在痴呆和衰老中的活体，并了解临床 FTLD-TDP病理的后果。随着对TDP相关疾病机制的更深入了解- 43病理学，翻译工作将填补体内诊断和预后方面的主要空白。管理核心A是 旨在为科学基金提供行政支持，包括监管和财务管理 本项目小组的五个项目和四个核心提出的工作，协调这些项目和核心之间的互动 通过由项目组成的内部执行委员会(IEC)开展多学科项目和核心工作 领导者(PLS)和核心领导者(CLS)，确保年度目标在 外部专家咨询委员会(EAC)与NIA工作人员一起，传播和协调我们的工作 与宾夕法尼亚大学(宾夕法尼亚大学)内外的其他科学家合作，让年轻科学家参与研究 调查TDP-43，并向患有FTLD-TDP相关疾病的患者和家属传播知识 精神错乱。我们通过七个具体目标实现这些目标。

Frontotemporal degeneration (FTD) is an understudied clinical neurodegenerative condition. Nevertheless, this is the most common dementia after Alzheimer disease (AD) in people younger than 65. The most common pathology associated with dementia in FTD is frontotemporal lobar degeneration (FTLD) due to transactive DNA binding protein of ~43 kD (TDP-43), known as FTLD-TDP. FTLD-TDP pathology is also found in ALS and many other conditions associated with aging including Limbic-predominant Age-related TDP-43 Encephalopathy (LATE). Since our discovery of FTLD-TDP in human disease, major gaps in understanding the pathophysiology and spread of human FTLD-TDP pathology and poor antemortem identification of patients with dementia due to TDP-43 pathology have been immense impediments to developing disease-modifying treatments that aim to target this pathology. In this Program Project Grant (PPG), we propose a novel and unique multidisciplinary research program focused on elucidating pathophysiologic mechanisms of human TDP-43 pathology, identifying FTLD-TDP in vivo in dementia and aging, and understanding the clinical consequences of FTLD-TDP pathology. With greater insight into mechanisms of disease associated with TDP- 43 pathology, translational work will fill major gaps in in vivo diagnosis and prognosis. Administrative Core A is designed to provide administrative support including regulatory and financial management for the scientific work proposed by the five Projects and four Cores of this PPG, coordinate the interaction of these multidisciplinary Projects and Cores through an Internal Executive Committee (IEC) consisting of the Project Leaders (PLs) and Core Leaders (CLs), ensure that annual goals are maintained with guidance from an External Advisory Committee (EAC) of experts together with NIA staff, disseminate and coordinate our work with other scientists at and beyond University of Pennsylvania (Penn), engage young scientists in research investigating TDP-43, and disseminate knowledge to patients and families who have FTLD-TDP-related disorders. We achieve these goals through seven Specific Aims.