ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)

摘要-ARTFL LEFFTDS纵向FTLD：总体部分 额颞叶变性(FTLD)是一组神经退行性疾病的主要术语 据信是由中枢神经系统中有毒蛋白质聚集体的积累引起的，最常见的是 由两种主要蛋白质之一-微管相关蛋白tau和TAR DNA结合蛋白组成 分子量为43 kDa。FTLD在年龄段以下的人群中至少与阿尔茨海默病(AD)一样常见 65.由于发病年龄较早，下降速度较快，FTLD被认为有更大的 与阿尔茨海默病相比，对患者和家属的生活产生了影响。至少20%的FTLD患者有 主要遗传性家族性疾病(f-FTLD)，而其余患者有零星FTLD 证候(S-FTLD)。额颞部退行性变(ARTFL； U54NS092089)研究登记并跟踪了这些S-FTLD患者。大约50%的f-FTLD是由 三种常见突变之一：微管相关蛋白tau(MAPT)、原颗粒蛋白(GRN)或 染色体9开放阅读框72(C9orf72)基因。家族性精神疾病的纵向评估现状 额颞叶痴呆受试者(LEFFTDS；U01 AG045390)研究登记并跟踪参与者 已知的家族突变，而ARTFL也登记那些有很强家族史但没有已知突变的人。这个 ARTFL LEFFTDS纵向额颞叶变性(ALLFTD)协议代表了我们的 计划正式合并ARTFL和LEFFTDS研究，以创建一个一体化的北美 研究FTLD的研究联盟。通过这一U19机制实施的ALLFTD计划将 通过创建七个核心改进我们的基础设施，以全面收集和共享数据。 我们解决了国家阿尔茨海默氏症项目法案(NAPA)指导委员会建议的主要目标 关于阿尔茨海默病相关痴呆(ADRD)通过这些核心和两个核心关注FTLD 研究项目。ALLFTD将支持许多额外的项目，以解决临床和 NAPA ADRD建议的神经科学目标，提供临床数据、扫描和生物样本 科学界。虽然没有有效的治疗FTLD疾病的方法，但越来越多的 新的潜在疗法正在进入临床试验。ALLFTD计划对支持数据的承诺 收集并与世界各地的研究人员分享将促进疾病修改疗法的开发 FTLD。

ABSTRACT – ARTFL LEFFTDS Longitudinal FTLD: OVERALL SECTION Frontotemporal Lobar Degeneration (FTLD) is the overarching term for a group of neurodegenerative disorders that are believed to be caused by the accumulation of toxic protein aggregates in the CNS, most commonly comprised of one of two major proteins–microtubule associated protein tau and TAR DNA binding protein molecular weight 43 kDa. FTLD is at least as common as Alzheimer's disease (AD) in those under the age of 65. Due to the earlier age of onset and the rapid rate of decline, FTLD is thought to have an even greater impact on the lives of patients and families when compared to AD. At least 20% of all FTLD patients have a dominantly inherited familial disorder (f-FTLD), whereas the remaining patients have a sporadic FTLD syndrome (s-FTLD). The current Advancing Research and Treatment in Frontotemporal Degeneration (ARTFL; U54 NS092089) study enrolls and follows these s-FTLD patients. Approximately 50% of f-FTLD is the result of one of three common mutations: the microtubule associated protein tau (MAPT), progranulin (GRN), or chromosome 9 open reading frame 72 (C9orf72) genes. The current Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS; U01 AG045390) study enrolls and follows participants with a known family mutation, while ARTFL also enrolls those with strong family histories but no known mutation. The ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) protocol represents our plan to formalize the merger of the ARTFL and LEFFTDS studies to create an integrated North American research consortium to study FTLD. The ALLFTD program, as implemented through this U19 mechanism, will improve our infrastructure for comprehensive collection and sharing of data through creation of seven cores. We address the main goals recommended by the National Alzheimer's Project Act (NAPA) Steering Committee on the Alzheimer's Disease-Related Dementias (ADRD) focused on FTLD through these cores and two research projects. ALLFTD will support many additional projects that address both the clinical and neuroscientific goals recommended by NAPA ADRD by providing clinical data, scans and biological samples to the scientific community. While there are no effective treatments for any FTLD disorder, increasing numbers of new potential therapies are entering clinical trials. The ALLFTD program's commitment to supporting data collection and sharing with researchers worldwide will foster development of disease-modifying therapies for FTLD.