Administrative Core

额颞叶变性（FTD）是一种研究不足的临床神经退行性疾病。但这 是65岁以下人群中仅次于阿尔茨海默病（AD）的最常见痴呆症。最常见的 FTD中与痴呆相关的病理学是由于交互性脑缺血引起的额颞叶变性（FTLD）。 ~43 kD的DNA结合蛋白（TDP-43），称为FTLD-TDP。FTLD-TDP病理学也见于ALS， 许多其他与衰老相关的疾病，包括与边缘相关的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FTLD-TDP的主要差距已经缩小。 人类FTLD-TDP病理学的病理生理学和传播以及患者的死前鉴定不佳 由于TDP-43病理学导致的痴呆症已经成为开发疾病修饰的巨大障碍， 针对这种病理的治疗方法。在这项计划项目补助金（PPG），我们提出了一个新的和 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病理学，在痴呆和衰老中体内鉴定FTLD-TDP，并了解其临床意义。 FTLD-TDP病理学的后果。随着对TDP相关疾病机制的深入了解， 43病理学，翻译工作将填补体内诊断和预后的主要空白。行政核心A是 旨在提供行政支持，包括监管和财务管理， 本PPG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相互作用。 多学科项目和核心通过内部执行委员会（IEC）组成的项目 领导者（PL）和核心领导者（CL），确保年度目标在 由专家组成的外部咨询委员会（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（Penn）内外的其他科学家一起，让年轻科学家参与研究 调查TDP-43，并向FTLD-TDP相关患者及家属宣传相关知识 紊乱我们通过七个具体目标来实现这些目标。

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.