The UK GENetic Frontotemporal dementia Initiative (UK GENFI)

额颞叶痴呆（FTD）是青年痴呆的常见原因。它对有年轻家庭的劳动适龄人口的影响是社会的重大健康和经济负担。目前唯一已知的FTD风险因素是遗传性的，三种基因（称为颗粒蛋白前体、tau和9号染色体开放阅读框72）中存在异常（突变），这三种基因占家族性FTD的大多数。现在有治疗这些疾病的有希望的途径，但我们仍然不知道什么时候应该开始药物治疗，或者我们应该如何衡量对治疗的反应。这项研究调查了患有遗传性（遗传性）FTD的人，包括已经出现症状的人以及他们的一级亲属，他们携带基因突变的风险为50%，因此将来会出现症状。通过研究携带疾病突变并因此注定要发展疾病的个体，我们可以从最早的变化中了解发展，这将是在人保持健康的同时开始任何治疗的最佳时间。该研究在2011年至2014年的试点阶段为研究遗传FTD和标准化测试方案创建了一个通用平台。本研究在试点阶段的基础上，在未来5年内创建一项英国范围内的遗传FTD研究（在伦敦大学学院、剑桥大学、曼彻斯特大学和牛津大学）。预计将有200名与会者参加，共接受三次评估。研究参与者将接受心理测试（记忆、语言、行为等测试），脑成像、血液检查和脊髓液收集（通过腰椎穿刺），以便研究这些不同测试在疾病的不同阶段的变化模式。该研究的主要成果是（1）提高对遗传性FTD中大脑系统如何分解以及这种分解如何与潜在的行为和认知症状相关的理解，（2）开发有助于在早期阶段识别疾病的标记物，以及（3）开发允许跟踪疾病进展的标记物。最终的目标将是在未来的遗传FTD药物临床试验中使用这些标记。该项目的结果还将改善遗传性FTD的识别和诊断，并为患者及其家庭成员提供更好的预后信息。

Frontotemporal dementia (FTD) is a common cause of young onset dementia. Its effect on people of working age with young families represents a major health and economic burden on society. The only known risk factors for FTD at present are genetic with abnormalities (mutations) in three genes accounting for the majority of familial FTD, called progranulin, tau and chromosome 9 open reading frame 72. There are now promising avenues for treatment of these disorders but we still do not know when drugs should be started or how we should measure the response to treatment. This study investigates people who have genetic (inherited) FTD, including both people who have developed symptoms and also their first-degree relatives who are at 50% risk of carrying the genetic mutation and therefore developing symptoms in the future. By studying individuals who carry the disease mutation and are thus destined to develop the disease we can understand the development from the very earliest changes, which would be the best time to start any treatment whilst the person remains well. A pilot phase of the study between 2011 and 2014 has created a common platform for studying genetic FTD and a standardized testing protocol. This study builds on the pilot phase by creating a UK-wide study of genetic FTD (at University College London, University of Cambridge, University of Manchester and the University of Oxford) over the next five years. It is expected that 200 participants will be seen, being assessed three times in total. Study participants will have psychology testing (tests of memory, language, behaviour etc.), brain imaging, blood tests and spinal fluid collection (by lumbar puncture) in order to investigate the patterns of change in these different tests at different stages of the disorder. The key outcomes of the study are to (1) improve understanding of how brain systems break down in genetic FTD and how this breakdown relates to the underlying behavioural and cognitive symptoms, (2) develop markers which help identify the disease at its earliest stage, and (3) develop markers that allow the progression of the disease to be tracked. The eventual aim will be to use these markers in future clinical trials of drugs in genetic FTD. The results of this project will also lead to improvement in the recognition and diagnosis of genetic FTD as well as provide improved information about prognosis for patients and members of their family.