Natural History of Amyloid Deposition in Adults with Down Syndrome

唐氏综合症成人淀粉样蛋白沉积的自然史

• 批准号: 7650587
• 负责人: BENJAMIN L HANDEN
• 金额: $ 81.19万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7650587
• 关键词: Adult; Affect; Age; Age-Years; Alleles; Alzheimer' s Disease; Amyloid; Amyloid deposition; Area; Autopsy; Brain; Caring; Chromosomes, Human, Pair 21; Clinical; Clinical Trials; Code; Cognition; Cognitive; Data; Deposition; Down Syndrome; Family; Family history of; Foundations; Functional disorder; Funding; Future; Gene Proteins; General Hospitals; General Population; Grant; High Prevalence; Human; Image; Individual; Life; Massachusetts; Measures; Medical; Natural History; Nature; Outcome; Pathology; Performance; Pittsburgh Compound-B; Population; Positron-Emission Tomography; Protein Precursors; Quality of life; Recruitment Activity; Research; Risk Factors; Sampling; Sorting - Cell Movement; Symptoms; Testing; Time; Tracer; Universities; apolipoprotein E-4; cohort; cost; high risk; in vivo; preclinical study

Our research group at the University of Pittsburgh has recently developed a promising, non-invasive, in vivo PET tracer for imaging amyloid deposition in living humans. Known as Pittsburgh Compound-B (PiB), it has shown much promise in documenting pre-symptomatic amyloid deposition in living subjects destined to develop Alzheimer's disease (AD). PiB also provides a means to determine the natural history of amyloid deposition. While there has been increasing use of PiB to assess amyloid deposition in cognitively normal individuals, the fact remains that despite identifiable risk factors that increase the likelihood of acquiring AD (e.g., age, family history, ApoE4), we cannot identify with certainty those who will develop AD. This makes the study of pre-clinical amyloid deposition difficult in the general population. Conversely, individuals with Down syndrome (DS) are at high risk for developing AD due to the presence of an extra copy of chromosome 21, which codes for the Af3 precursor protein (APP) gene. Postmortem studies have documented the presence of AD pathology in 60 to 90% of adults with DS (with greater pathology increasing with age)(Sylvester, 1984; Wisniewski et aI., 1985). Additionally, symptoms of AD occur in over 40% for DS individuals between 50 and 59 years of age (Hyman, 1992; Schupf et aI., 1998). Thus, the study of adults with DS provides a valuable opportunity to follow the natural history of amyloid deposition and compare it to clinical symptomatology - knowing that approximately half of the group will eventually develop clinical AD and an even greater fraction will develop amyloid deposits. Toward that end, the current multi-center proposal (University of Pittsburgh and Massachusetts General Hospital) will document amyloid deposition in 64 nondemented/ functionally stable adults with DS over a two-year period. We will study three age cohorts: 30-39 yrs, 40-49 yrs and .2:.50 yrs. Subjects will also be assessed for the presence ofthe apolipoprotein-E4 (ApoE4) allele to determine its possible association with accelerated deposition brain amyloid. While we will not complete a natural history study of amyloid deposition in DS during the current project period, this effort will lay the foundation by gathering a valuable cohort of PiB+, non-demented DS subjects that we can follow beyond this grant period with future funding.

我们在匹兹堡大学的研究小组最近开发了一个有前途的， 无创的，体内宠物示踪剂，用于成像活着的人类淀粉样蛋白沉积。 它被称为匹兹堡化合物B（PIB），它在记录文献中表现出了很多希望 活在活的受试者中的症状前淀粉样蛋白沉积物注定要发展阿尔茨海默氏症 疾病（AD）。 PIB还提供了确定淀粉样蛋白自然历史的手段 沉积。虽然越来越多地使用PIB来评估淀粉样蛋白沉积 认知正常人，事实仍然是，尽管可识别的风险因素 增加获取广告的可能性（例如，年龄，家族史，APOE4），我们不能 确定那些将开发广告的人。这使得临床前的研究 普通人群中的淀粉样蛋白沉积困难。相反，个人 唐氏综合症（DS）由于存在额外 染色体21的副本，该染色体编码为AF3前体蛋白（APP）基因。验尸 研究已经记录了60％至90％的成年人的AD病理 随着DS（随着年龄的增长而增加病理学）（Sylvester，1984； Wisniewski et ai。， 1985）。此外，DS个体在40％之间出现AD的症状在40％以上 和59岁（Hyman，1992; Schupf et ai。，1998）。 因此，对DS的成年人的研究为遵循淀粉样蛋白沉积的自然历史提供了宝贵的机会，并将其与临床症状相提并论 - 知道该组的大约一半最终会发展临床广告，并且更大的部分将发展淀粉样蛋白。 沉积物。为此，目前的多中心提议（匹兹堡大学 和马萨诸塞州综合医院）将记录64个无材的淀粉样沉积/ 功能稳定的成年人在两年内具有DS。我们将研究三个 年龄人群：30-39岁，40-49岁和.2：.50岁。也将对受试者进行评估 载脂蛋白-E4（APOE4）等位基因的存在以确定其可能的关联 加速沉积脑淀粉样蛋白。虽然我们不会完成自然历史 在当前项目期间DS中淀粉样蛋白沉积的研究，这项工作将进行 基金会通过收集宝贵的PIB+队列，非痴呆的DS主题 我们可以超越这个赠款期，并提供未来的资金。