Aging of Frontal Structure and Function in Down Syndrome and Dementia

项目总结/摘要 唐氏综合征（DS）是人类智力残疾的主要原因，据估计， 在美国有超过30万人患有这种遗传疾病。几乎所有DS 个体在其40岁时具有足以诊断AD的神经病理学。然而，在这方面， 痴呆症可能直到十年后才发展，有些人的认知能力仍然完好无损。 因此，我们试图在5年内跟踪一组年龄在20-40岁之间的成年人 时间来确定年龄和痴呆相关的认知变化，特别是关注 额叶功能我们有四个目标。目标1将从认知上描述一个队列， 患有DS的成年人，并对个体进行为期5年的随访。AIM 2将使用磁共振技术 成像以测量纵向随访人群中每年的白色物质完整性。 目标3将分析每年从队列中抽取的血浆并测量信号蛋白的变化 以确定AD发展的生物标志物，这些生物标志物也与认知相关。目标4将 研究DS成人的存档和新尸检大脑样本，以确定分子途径 在AD发生之前和发生期间发生变化。拟议研究的结果将 有助于开发非侵入性生物标志物，这将有助于早期AD诊断， DS和监测疾病进展。此外，还发现了机制上相关的新生物标志物， AD神经病理学和痴呆症也将为未来的设计提供结果。 治疗或预防DS痴呆的临床试验。

Project Summary/Abstract Down syndrome (DS) is the major cause of intellectual disability in humans and it is estimated there are over 300,000 individuals with this genetic disorder in the United States. Virtually all DS individuals have sufficient neuropathology for a diagnosis of AD in their 40th year. However, dementia may not develop until up to a decade later and some people remain cognitively intact. Thus, we seek to follow a group of adults ranging in age from 20-40 years over a 5 year period of time to identify age and dementia-associated changes in cognition and in particular focus on frontal lobe function. Our aims are four-fold. Aim 1 will cognitively characterize a cohort of adults with DS and follow individuals for a period of 5 years. Aim 2 will use magnetic resonance imaging to measure white matter integrity on an annual basis in longitudinally followed people. Aim 3 will assay plasma drawn annually from the cohort and measure signaling protein changes to identify biomarkers of AD development and that are also correlated with cognition. Aim 4 will study archived and new autopsy brain samples from DS adults to identify molecular pathways that change prior and during AD development. The outcomes of the proposed studies will contribute to the development of noninvasive biomarkers that will assist in early AD diagnosis in DS and monitor disease progression. Further, novel biomarkers that are mechanistically related to aging, AD neuropathology and dementia will also provide outcomes for the design of future therapeutic clinical trials to treat or prevent dementia in DS.