The UK GENetic Frontotemporal dementia Initiative (UK GENFI)

额颞性痴呆(FTD)是青年起病痴呆的常见原因。它对有年轻家庭的工作年龄的人的影响是对社会的重大健康和经济负担。目前唯一已知的FTD的危险因素是遗传，有三个基因的异常(突变)占家族性FTD的大部分，称为原颗粒蛋白、tau和染色体9开放阅读框架72。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用药，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(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，他们有50%的风险携带基因突变，因此未来会出现症状。通过研究携带疾病突变并因此注定会患上这种疾病的人，我们可以从最早的变化中了解疾病的发展，这将是在人保持健康的情况下开始任何治疗的最佳时机。2011至2014年间，该研究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。这项研究在试点阶段的基础上，在未来五年内在英国范围内(伦敦大学学院、剑桥大学、曼彻斯特大学和牛津大学)创建了一项关于遗传FTD的研究。预计将有200名参与者参加，总共接受三次评估。研究参与者将接受心理测试(记忆力、语言、行为等测试)、大脑成像、血液测试和脊髓液采集(通过腰椎穿刺法)，以调查这些不同测试在疾病不同阶段的变化模式。这项研究的关键成果是：(1)提高对大脑系统如何在遗传FTD中崩溃以及这种崩溃如何与潜在的行为和认知症状有关的理解，(2)开发有助于在疾病的早期阶段识别疾病的标记，以及(3)开发能够跟踪疾病进展的标记。最终目标是将这些标记用于未来治疗遗传性FTD的药物的临床试验。该项目的结果还将有助于改善对遗传性FTD的认识和诊断，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.