Aging of Frontal Structure and Function in Down Syndrome and Dementia

项目摘要/摘要 唐氏综合症(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性疾病。几乎所有DS 个体在40岁时有足够的神经病理诊断为AD。然而， 痴呆症可能要到十年后才会发展，一些人的认知能力仍然完好无损。 因此，我们寻求在5年内跟踪一组年龄在20-40岁之间的成年人 确定年龄和痴呆症相关认知变化的时间，并特别关注 额叶功能。我们的目标有四个方面。目标1将从认知上描述一群 患有DS的成人，并对个体进行为期5年的追踪。Aim 2将使用磁共振 在纵向跟踪的人中，每年进行成像以测量白质完整性。 AIM 3将检测每年从队列中提取的血浆并测量信号蛋白的变化 寻找阿尔茨海默病发生的生物标志物以及与认知相关的生物标志物。目标4将 研究DS成人的存档和新的尸检脑样本以确定分子途径 这在AD开发之前和开发过程中都会发生变化。拟议研究的结果将 有助于开发有助于AD早期诊断的非侵入性生物标志物 DS和监测疾病进展。此外，与机械相关的新型生物标记物 对于衰老，AD的神经病理和痴呆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.