Neuropathology & Genetics Core

神经病理学

基本信息

批准号：
10261335
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
项目类别：
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/10261335
关键词：
Affect Aging Alzheimer&apos 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 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

项目摘要

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) 是一种尚未充分研究的临床神经退行性疾病，甚至尽管它是 65 岁以下人群中继阿尔茨海默氏病 (AD) 后导致痴呆的最常见原因。与 FTD 相关的最常见额颞叶变性 (FTLD) 病理是 TDP-43 蛋白质病称为 FTLD-TDP，另一类主要包括 FTLD-Tau 病例。一些常染色体显性基因突变和与疾病相关的遗传变异相关除了与 FTLD 特定亚型相关的基因突变外，没有任何其他因素与 FTD 相关。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具有 FTLD-TDP 组织病理学的患者来自具有 FTLD-Tau 病理学的患者，也来自患有 FTLD-Tau 病理学的患者具有临床 FTD，但不是病理性 AD 的典型，神经病理学和遗传学核心将发挥作用。与其他核心和项目一起提高我们对与 TDP 相关的多级退化的理解该项目资助项目（PPG）中检查的神经网络将执行全面的后处理。尸检脑部尸检，为临床后续病例提供明确的尸检诊断核心B和神经影像核心C。我们还将对病例进行全面的基因分析，识别致病原因和相关基因变化的控制措施将包括银行库。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 表达研究以进一步实现 PPG 研究项目的目标。