Neuropathology & Genetics Core

额颞部退行性变(FTD)是一种临床上研究甚少的神经退行性疾病 虽然它是继阿尔茨海默病(AD)之后65岁人群中导致痴呆症的最常见原因。这个 与FTD相关的最常见的额颞叶变性(FTLD)病理是TDP-43 蛋白质病称为FTLD-TDP，另一大类是FTLD-Tau病例。此外， 几个常染色体显性基因突变和与疾病相关的遗传变异相关 使用FTD。除了与FTLD特定亚型相关的基因突变外，没有 绝大多数患有散发性疾病的FTD患者的已知生物标志物可以可靠地区分 FTLD-TDP组织病理学患者来自FTLD-Tau病理患者，也不来自 临床上有FTD，但都是病理性AD的非典型变种。神经病理学和遗传学的核心将会奏效 与其他核心和项目一起提高我们对TDP相关多水平退行性变的理解 本计划项目拨款(PPG)中考察的神经网络。这一核心将执行全面的后处理- 验尸脑部检查，为临床随访病例提供明确的尸检诊断 核心B和神经成像核心C。我们还将对病例和 确定致病原因和相关基因变化的对照方法。其他活动将包括银行业务 组织和核酸，为其他研究人员提供组织、数据和专业知识，并进行RNA 表达研究，以促进PPG研究项目的目标。

Frontotemporal degeneration (FTD) is an understudied clinical neurodegenerative condition even though it is the most common cause of dementia after Alzheimer’s disease (AD) in people <65 years old. The most common frontotemporal lobar degeneration (FTLD) pathology associated with FTD is TDP-43 proteinopathy known as FTLD-TDP with the other major class consisting of cases of FTLD-Tau. Moreover, several autosomal dominant gene mutations and disease-associated genetic variants have been associated with FTD. Aside from genetic mutations that are associated with specific subtypes of FTLD, there are no known biomarkers for the vast majority of FTD patients with sporadic disease that can reliably distinguish patients with FTLD-TDP histopathology from those with FTLD-Tau pathology, nor from patients who present with clinical FTD but are atypical variants of pathological AD. The Neuropathology & Genetics Core will work with other cores and projects to improve our understanding of the TDP-related degeneration of multilevel neural networks examined in this Program Project Grant (PPG). This core will perform a comprehensive post- mortem brain autopsy examination to provide a definitive autopsy diagnosis for cases followed in the clinical core B and the neuroimaging core C. We will also perform a comprehensive genetic analysis of cases and controls to identify disease causing and associated genetic changes. Additional activities will including banking of tissues and nucleic acids, providing tissues, data and expertise to other investigators, and conducting RNA expression studies to further the aims of the research projects in the PPG.