Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)

阿尔茨海默病生物标志物联盟 - 唐氏综合症 (ABC-DS)

• 批准号: 10037875
• 负责人: Bradley T Christian
• 金额: $ 2098.04万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10037875
• 关键词: Adult; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer' s disease therapeutic; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Attitude; Autopsy; Biological Markers; Biology; Biometry; Caring; Chromosome 21; Clinical; Clinical Trials; Clinical Trials Design; Cognitive; Communities; Data; Data Analyses; Data Collection; Dementia; Development; Disease; Disease Progression; Down Syndrome; Event; Family; Functional disorder; Funding; General Population; Genes; Genetic; Genetic Markers; Genetic Risk; Goals; Health Promotion; Image; Incidence; Individual; Inflammation; Infrastructure; Intervention; Laboratories; Late Onset Alzheimer Disease; Lead; Life; Liquid substance; Longevity; Measures; Medical; Minority Recruitment; Modality; Nerve Degeneration; Neuropsychology; Outcome; Participant; Pathogenicity; Pathologic; Phenotype; Policies; Population; Prevalence; Prevention; Proteomics; Public Health; Quality of life; Research; Research Institute; Research Personnel; Risk; Risk Assessment; Senile Plaques; Siblings; Specimen; Staging; Structure; Testing; Translating; Translations; Underrepresented Minority; United States National Institutes of Health; aging population; cerebrovascular pathology; cohort; cost; data management; disease phenotype; endophenotype; genetic variant; genome sequencing; high risk; high risk population; imaging biomarker; improved; metabolomics; multimodality; neuroimaging; neuropathology; next generation; novel; novel marker; outreach; overexpression; pre-clinical; precision medicine; prevent; programs; recruit; repository; sex; success; tau Proteins; translational research program; virtual; whole genome

Overall Abstract Alzheimer disease (AD) is the most common cause of dementia in the general population and the numbers of people living with the disease are rising exponentially. A similar event is occurring in the community of people with Down syndrome (DS) due, in part, to genetic risk (trisomy 21 and lifelong overexpression of APP) leading to overproduction of Aβ, combined with longer lifespans. The study of DS affords an opportunity to understand the timing and sequence of pathological changes associated with AD. An overarching theme of the Alzheimer’s Biomarkers Consortium – Down Syndrome (ABC-DS) is to characterize AD in DS, an issue of major and growing significance. Data generated from ABC-DS are necessary to determine if the AD pathological cascade is the same between DS and late onset AD (LOAD) or whether the pathogenic staging has distinct features. Parallels between the two highlights the importance of research with people with DS for advancing our overall understanding of AD, which in turn can form the basis for clinical trials. To that end, ABC-DS assembles an exceptional and highly collaborative research team that will follow a cohort of people with DS to test hypotheses related to 1) how AD in DS may parallel sporadic AD within an amyloid, tau, neurodegeneration AT(N) framework and to identify modifiers of risk of conversion/progression (Project 1); 2) to identify genetic modifiers of the development of AD in DS (Project 2); and 3) to translate outcomes to a precision medicine framework and expedite clinical trials (Project 3). We will acquire harmonized clinical and neuropsychological outcomes (Clinical Core), neuroimaging outcomes (Neuroimaging Core), bio-fluids and genetics measures (Omics Core) and neuropathology data from autopsy (Neuropathology Core). To rapidly disseminate information to our DS communities and to engage underrepresented minorities, we have a Core dedicated to outreach, recruitment and retention (ADDORE Core). Lastly, to build upon nationwide efforts to identify targets for interventions to slow or prevent AD, our Biostatistics and Data Management Core will make high quality data from all aspects of our study available to qualified researchers by distributing outcomes through LONI and ATRI. Following the lead of outstanding established AD networks (ADNI, DIAN), ABC-DS will make a significant contribution to national efforts to improve the quality of life of our aging population through advancing progress toward effective prevention and treatment of AD.

总体抽象 阿尔茨海默氏病（AD）是普通人群中痴呆的最常见原因，数量 患有这种疾病的人正在成倍增长。人民社区也发生了类似的事件 唐氏综合症（DS）部分归因于遗传风险（三体性21和应用程序的终身表达）。 过量生产Aβ，结合寿命更长。对DS的研究提供了一个理解的机会 与AD相关的病理变化的时间和顺序。阿尔茨海默氏症的总体主题 生物标志物联盟 - 唐氏综合症（ABC-DS）是在DS中表征AD，这是一个主要和增长的问题 意义。从ABC-DS产生的数据是必要的，以确定AD病理级联是否是 DS和晚期AD（负载）之间相同，或者致病性分期是否具有不同的特征。相似之处 在这两个之间，强调了与DS的人进行研究的重要性，以促进我们的整体 对AD的了解，这又可以构成临床试验的基础。为此，ABC-DS组装了 杰出且高度协作的研究团队将跟随一群DS人群来检验假设 与1）DS中的AD在（N）框架处的淀粉样蛋白，TAU，神经变性中的AD如何平行 并确定转化/进展风险的修饰符（项目1）； 2）确定遗传修饰符 DS中的AD开发（项目2）； 3）将结果转化为精确的医学框架和 加快临床试验（项目3）。我们将获得统一的临床和神经心理学结果（临床） 核心），神经成像结果（神经影像学核心），生物流体和遗传学措施（Omics Core）和 尸检（神经病理学核心）的神经病理学数据。快速向我们的DS传播信息 社区并参与代表性不足的少数群体，我们有一个致力于外展，招聘的核心 和保留（附加核心）。最后，以全国范围的努力为基础，以确定干预措施的目标 或防止广告，我们的生物统计学和数据管理核心将从我们的各个方面获得高质量的数据 通过LONI和ATRI分发结果，可以为合格的研究人员提供研究。遵循 杰出的已建立广告网络（ADNI，DIAN），ABC-DS将为国家做出重大贡献 通过提高进步朝着有效的进步来改善人口老龄化的生活质量的努力 预防和治疗AD。