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: 10454250
• 负责人: Bradley T Christian
• 金额: $ 1923.36万
• 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/10454250
• 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; Persons; 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; middle age; 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) 是一般人群中导致痴呆症的最常见原因， 患有这种疾病的人数呈指数级增长。类似的事件也在民间发生 患有唐氏综合症 (DS) 的部分原因是遗传风险（21 三体性和 APP 终生过度表达）导致 Aβ 的过量产生以及更长的寿命。 DS 的研究提供了一个了解 与 AD 相关的病理变化的时间和顺序。阿尔茨海默氏症的首要主题 生物标志物联盟 – 唐氏综合症 (ABC-DS) 旨在描述 DS 中的 AD，这是一个重大且日益增长的问题 意义。 ABC-DS 生成的数据对于确定 AD 病理级联是否是 AD 病理级联所必需的。 DS 和迟发性 AD (LOAD) 之间是否相同，或者致病性分期是否具有不同的特征。相似之处 两者之间的关系凸显了与 DS 患者进行研究对于推进我们整体发展的重要性 对 AD 的了解，进而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踪一群 DS 患者来检验假设 与 1) DS 中的 AD 如何与淀粉样蛋白、tau 蛋白、神经变性 AT(N) 框架内的散发性 AD 相似 并确定转化/进展风险的修正因素（项目 1）； 2) 鉴定基因修饰因子 DS 中 AD 的开发（项目 2）； 3) 将结果转化为精准医学框架 加快临床试验（项目 3）。我们将获得协调一致的临床和神经心理学结果（临床 核心）、神经影像结果（神经影像核心）、生物体液和遗传学测量（组学核心）和 来自尸检的神经病理学数据（神经病理学核心）。快速向我们的 DS 传播信息 社区并吸引代表性不足的少数群体，我们有一个核心致力于外展、招聘 和保留（ADDORE 核心）。最后，以全国范围内的努力为基础，确定干预措施的目标，以减缓 或预防AD，我们的生物统计和数据管理核心将从我们的各个方面产生高质量的数据 通过 LONI 和 ATRI 分发结果，向合格的研究人员提供研究结果。跟随 ABC-DS 已建立的杰出 AD 网络（ADNI、DIAN）将为国家做出重大贡献 通过推进有效的进展，努力改善老龄化人口的生活质量 AD 的预防和治疗。