Neuropathology & Genetics Core

神经病理学

基本信息

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
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/10454267
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 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

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.

额颞变性（FTD）甚至是一种理解的临床神经退行性疾病尽管这是阿尔茨海默氏病（AD）的最常见原因在<65岁的人中。这与FTD相关的最常见的额颞叶变性（FTLD）病理是TDP-43 蛋白质疗法称为FTLD-TDP，其他主要类别由FTLD-TAU病例组成。而且，几种常染色体显性基因突变和与疾病相关的遗传变异已经相关与FTD。除了与FTLD的特定亚型相关的基因突变外，没有绝大多数FTD患有零星疾病的FTD患者的已知生物标志物，可以可靠地区分患有FTLD-TAU病理患者的FTLD-TDP组织病理学患者，也不是来自出现的患者具有临床FTD，但是病理AD的非典型变体。神经病理学和遗传学核心将起作用与其他核心和项目一起，以提高我们对与TDP相关的多级变性的理解在此计划项目赠款（PPG）中检查的神经网络。该核心将执行全面的职位 - Mortem脑尸检检查，为临床的病例提供明确的尸检诊断核心和神经成像核心C.我们还将对病例和对照以识别引起疾病的疾病和相关的遗传变化。其他活动将包括银行组织和核酸，向其他研究者提供组织，数据和专业知识，并进行RNA 表达研究以进一步在PPG中的研究项目的目标。