Natural History of Amyloid Deposition in Adults with Down Syndrome

我们匹兹堡大学的研究小组最近开发出了一种很有前途的 活体非侵入性PET示踪剂，用于成像活体人类的淀粉样蛋白沉积。 它被称为匹兹堡化合物-B(PIB)，在记录方面显示出很大的潜力 阿尔茨海默病患者的症状前淀粉样蛋白沉积 疾病(AD)。PIB还提供了一种确定淀粉样蛋白自然病史的方法 证词。虽然越来越多地使用PIB来评估淀粉样蛋白在脑内的沉积 认知正常的人，事实仍然是，尽管可识别的风险因素 增加患AD的可能性(例如，年龄、家族史、ApoE4)，我们不能 确定哪些人会患上AD。这使得临床前研究成为可能。 淀粉样蛋白在普通人群中沉积困难。相反，拥有 唐氏综合征(DS)是发生AD的高风险因素，因为存在额外的 21号染色体的拷贝，编码Af3前体蛋白(APP)基因。尸检 研究证明，60%至90%的成年人存在AD病理 DS(随着年龄的增长，更严重的病理改变)(Sylvester，1984；Wisniewski et Ai.， 1985年)。此外，在50岁之间的DS患者中，超过40%的人会出现AD症状 59岁(Hyman，1992；Schupf et Ai，1998)。 因此，对成年DS患者的研究提供了一个宝贵的机会来跟踪淀粉样蛋白沉积的自然历史，并将其与临床症状学进行比较-知道大约一半的患者最终将发展为临床AD，而更大比例的人将发展为淀粉样蛋白 押金。为此，目前的多中心提案(匹兹堡大学 和马萨诸塞州总医院)将记录非痴呆/淀粉样蛋白沉积 在两年的时间里，患有DS的成年人功能稳定。我们将研究三个方面 年龄组：30-39岁，40-49岁和.2：.50岁。受试者也将被评估为 载脂蛋白-E4(ApoE4)等位基因的存在以确定其可能的关联 大脑淀粉样蛋白加速沉积。虽然我们不会完成一部自然历史 在当前项目期间，DS中淀粉样蛋白沉积的研究，这项工作将 基金会通过收集PIB+的、非痴呆的DS受试者的宝贵队列 我们可以在此授权期之后继续提供未来的资金。

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.