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.

总体摘要 阿尔茨海默病(AD)是普通人群中导致痴呆的最常见原因， 患有这种疾病的人呈指数级增长。类似的事件也在人们的社区中发生 唐氏综合征(DS)的部分原因是遗传风险(21三体和APP终身过度表达)导致 Aβ生产过剩，再加上更长的寿命。DS的研究提供了一个机会来理解 阿尔茨海默病与阿尔茨海默病相关的病变的时间和顺序阿尔茨海默氏症的主要主题 生物标记物联合唐氏综合症(ABC-DS)是对DS患者中AD的特征，这是一个主要的和不断增长的问题 意义。从ABC-DS生成的数据是确定AD病理性级联是否为 DS和晚发性AD(LOAD)之间是否有相同的病原学分期有明显的特点。Parallels 两者之间的关系突出了与DS患者进行研究对于推进我们的整体 对阿尔茨海默病的了解，这反过来可以形成临床试验的基础。为此，ABC-DS组装了一个 杰出且高度协作的研究团队，将跟踪一群患有DS的人来测试假设 与1)DS中的AD如何平行于淀粉样蛋白、tau、神经变性AT(N)框架内的散发性AD有关 以及确定转换/进展风险的修饰物(项目1)；2)确定 在DS中开发AD(项目2)；以及3)将成果转化为精确医学框架和 加快临床试验(项目3)。我们将获得协调的临床和神经心理结果(临床 核心)、神经成像结果(神经成像核心)、生物体液和遗传学措施(Omics核心)和 来自尸检的神经病理学数据(神经病理学核心)。向我们的DS快速传播信息 为了吸引代表人数不足的少数群体，我们有一个核心专门负责外联、招聘 和保留(ADDORE Core)。最后，在全国性努力的基础上，确定减缓干预的目标 或预防AD，我们的生物统计和数据管理核心将从我们的 通过LONI和ATRI分发结果，合格的研究人员可以获得的研究。继……之后 杰出的成熟AD网络(ADNI、DIAN)，ABC-DS将为国家 努力改善我们老龄化人口的生活质量，推进有效的进展 防治阿尔茨海默病。