Neuropathology & Genetics Core

神经病理学

• 批准号: 10454267
• 负责人: Edward Byung-Ha Lee
• 金额: $ 20.31万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10454267
• 关键词: Affect; Aging; Alzheimer' s Disease; Archives; Autopsy; Behavioral; Bioinformatics; Biological Markers; Biometry; Brain; C9ORF72; Cells; Clinical; Collaborations; Complex; DNA; DNA Library; DNA Sequence Alteration; Data; Data Storage and Retrieval; Databases; Dementia; Diagnosis; Disease; Dominant Genes; Exhibits; Frontotemporal Dementia; Frontotemporal Lobar Degenerations; Functional disorder; Gene Mutation; Genetic; Genetic Heterogeneity; Genetic Transcription; Goals; Heterogeneity; Histopathology; Individual; Language; Lead; Magnetic Resonance Imaging; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Nucleic Acids; Pathogenicity; Pathologic; Pathology; Patients; Persons; Program Research Project Grants; Proteins; Research Personnel; Research Project Grants; Resources; Risk; Risk Factors; Scientist; Single Nucleotide Polymorphism; Specimen; Subgroup; Syndrome; Tissue Sample; Tissues; Training; Variant; Work; brain tissue; case control; clinical phenotype; frontotemporal degeneration; genetic analysis; genetic variant; human old age (65+); improved; neural network; neuroimaging; neuropathology; protein TDP-43; risk variant; tau Proteins; treatment group

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.

额颞叶变性（FTD）是一种研究不足的临床神经退行性疾病， 尽管它是阿尔茨海默氏病（AD）后65岁以下人群中痴呆症的最常见原因。的 与FTD相关的最常见额颞叶变性（FTLD）病理学为TDP-43 蛋白质病称为FTLD-TDP，另一个主要类别由FTLD-Tau病例组成。此外，委员会认为， 一些常染色体显性基因突变和疾病相关的遗传变异已经与 关于FTD除了与FTLD特定亚型相关的基因突变外， 绝大多数散发性FTD患者的已知生物标志物，可可靠区分 具有FTLD-TDP组织病理学的患者与具有FTLD-Tau病理学的患者，也不与存在 但为病理性AD的非典型变体。神经病理学和遗传学核心将工作 与其他核心和项目，以提高我们对与TDP相关的多层次退化的理解， 本计划项目资助（PPG）中研究的神经网络。该核心将执行一个全面的后- 尸检脑尸检检查，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。我们还将对病例进行全面的遗传分析， 控制，以确定疾病的原因和相关的遗传变化。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。