Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) - KUMC Field Site Supplement

阿尔茨海默病生物标志物联盟 - 唐氏综合症 (ABC-DS) - KUMC 现场补充资料

• 批准号: 10844809
• 负责人: Bradley T Christian
• 金额: $ 77.49万
• 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/10844809
• 关键词: Abeta synthesis; 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 Precursor; Attitude; Autopsy; Biological Markers; Biology; Biometry; Caring; Chromosome 21; Clinical; Clinical Trials; Clinical Trials Design; Cognitive; Communities; Data; Data Analyses; Data Collection; Dedications; 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; Longevity; Measures; Medical; Minority Recruitment; Modality; Nerve Degeneration; Neuropsychology; Outcome; Participant; Pathogenicity; Pathologic; Persons; Phenotype; Policies; Population; Prevalence; Prevention; Proteomics; Public Health; Qualifying; Quality of life; Research; Research Institute; Research Personnel; Risk; Risk Assessment; Senile Plaques; Siblings; Site; 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; progression marker; 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）是一般人群中痴呆症的最常见原因， 患有这种疾病的人呈指数增长。一个类似的事件正在发生在社区的人 唐氏综合征（DS）部分原因是遗传风险（21三体和APP终身过度表达）， 导致Aβ分泌过多，寿命延长DS的研究提供了一个了解的机会 与AD相关的病理变化的时间和顺序。老年痴呆症的一个重要主题 生物标志物联盟-唐氏综合征（ABC-DS）是表征DS中的AD，这是一个重大且日益增长的问题。 意义从ABC-DS生成的数据对于确定AD病理级联反应是否是 DS和迟发性AD（LOAD）之间是否相同或致病分期是否具有不同特征。Parallels 两者之间的差异突出了与DS患者进行研究的重要性， 了解AD，这反过来又可以形成临床试验的基础。为此，ABC-DS组装了一个 一个杰出的、高度合作的研究团队，将跟踪一组DS患者，以测试假设 与1）DS中的AD如何在淀粉样蛋白、tau蛋白、神经变性AT（N）框架内与散发性AD平行有关 并确定转换/进展风险的修饰因子（项目1）; 2）确定 在DS中开发AD（项目2）;以及3）将结果转化为精确医学框架， 加快临床试验（项目3）。我们将获得协调的临床和神经心理学结果（临床 核心）、神经影像学结局（神经影像学核心）、生物液体和遗传学测量（组学核心），以及 尸检的神经病理学数据（神经病理学核心）。迅速向我们的DS发布信息 社区和参与代表性不足的少数民族，我们有一个核心致力于外展，招聘， 和保留（ADDORE核心）。最后，在全国努力确定干预目标的基础上， 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提供高质量的数据。 通过LONI和ATRI分发结果，向合格的研究人员提供研究。在...的带领下， 优秀的建立AD网络（ADNI，DIAN），ABC-DS将为国家做出重大贡献 努力通过推进有效的 AD的预防和治疗。

项目成果

Physical activity, memory function, and hippocampal volume in adults with Down syndrome.

• DOI: 10.3389/fnint.2022.919711
• 发表时间: 2022
• 期刊: FRONTIERS IN INTEGRATIVE NEUROSCIENCE
• 影响因子: 3.5
• 作者: Peven, Jamie C.;Handen, Benjamin L.;Laymon, Charles M.;Fleming, Victoria;Piro-Gambetti, Brianna;Christian, Bradley T.;Klunk, William;Cohen, Ann D.;Okonkwo, Ozioma;Hartley, Sigan L.
• 通讯作者: Hartley, Sigan L.