Core C: Clinical Core

临床核心摘要 几乎所有患有唐氏综合症(DS)的成年人都有与阿尔茨海默病相一致的神经病理变化 (AD)到40岁，包括弥漫性和神经性斑块中β淀粉样肽(Aβ)的沉积，大多数将 在他们快60岁的时候患上临床痴呆症。AD的高风险被归因于，至少在一定程度上是由于三重 和21号染色体上淀粉样前体蛋白(APP)基因的过度表达，导致 β多肽水平ABC-DS研究旨在了解病理生理和临床变化 在患有DS的成年人中，因为他们经历了AD从最早的临床前阶段到坦率的痴呆的进展。 临床核心的目的是为参与者提供DS(和兄弟姐妹对照)、临床数据和 生物标本，以实现每个项目的目标。这最终涉及到提供最佳实践配置文件 能力和健康状况，以得出有效的痴呆症临床分类。核心将承担 对720名个体进行纵向评估，以维持550名成年DS和DS患者的积极队列 50个兄弟控件。在这个为期五年的项目过程中，参与者将接受最多四次评估 (相隔16个月)。数据收集将包括神经心理评估、照顾者问卷 功能和可能的痴呆症症状，身体/神经检查，血液遗传学， 脂肪组学和蛋白质组学分析，MRI和PET扫描(淀粉样蛋白，tau，FDG)和LP。积累性临床 数据将全面输入ATRI数据库，以便进行相关分析 项目1-3中相同参与者产生的丰富生物数据。未来的临床数据将 形成了潜在生物标志物的横断面和纵向分析的基础，并将使表型 对于了解它们与疾病风险、发病、严重程度、进展和 症状。

Clinical Core Abstract Virtually all adults with Down Syndrome (DS) have neuropathological changes consistent with Alzheimer Disease (AD) by age 40, including deposition of β amyloid peptide (Aβ) in diffuse and neuritic plaques, and most will develop clinical dementia by their late 60s.The high risk for AD has been attributed, at least in part, to triplication and overexpression of the gene for amyloid precursor protein (APP) on chromosome 21, leading to elevated levels of Aβ peptides The ABC-DS study is designed to understand the pathophysiological and clinical changes in adults with DS as they experience progression of AD from its earliest preclinical stages through frank dementia. The purpose of the Clinical Core is to provide participants with DS (and sibling controls), clinical data, and biological specimens to enable the goals of each project. This ultimately involves providing a best practice profile of abilities and health status to arrive at a valid clinical classification of dementia status. The Core will undertake the longitudinal assessment of a cohort of 720 individuals to maintain an active cohort of 550 adults with DS and 50 sibling controls. Over the course of this five-year project, participants will be seen for up to four evaluations (separated by 16 months). Data collection will include neuropsychological evaluations, caregiver questionnaires of functioning and possible dementia symptoms, a physical/neurological examination, blood for genetics, lipidomics and proteomics analyses, MRI and PET scans (amyloid, tau, FDG) and LP. The accumulating clinical data will be entered comprehensively into the ATRI database so it can be available for correlative analyses with the rich biological data generated from the same participants in Projects 1-3. The prospective clinical data will form the basis of cross sectional and longitudinal analyses of potential biomarkers and will enable the phenotypic correlations essential to understanding how they relate to disease risk, onset, severity, progression, and symptoms.