Biomarkers of Alzheimer's Disease in Adults with Down Syndrome

患有唐氏综合症的成人中阿尔茨海默病的生物标志物

• 批准号: 9266766
• 负责人: IRA T. LOTT
• 金额: $ 390.35万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9266766
• 关键词: Activities of Daily Living; Adult; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Anisotropy; Archives; Atrophic; Basic Science; Biological; Biological Markers; Biometry; Blood; Blood Banks; Blood specimen; Brain; California; Candidate Disease Gene; Cerebrospinal Fluid; Classification; Clinical; Clinical Research; Clinical Trials; Cognitive; Corpus Callosum; DNA; Data; Dementia; Deterioration; Development; Developmental Disabilities; Diagnostic; Disease Pathway; Disease Progression; Down Syndrome; Evaluation; Foundations; Frequencies; Future; General Hospitals; Genes; Genetic Markers; Genetic Polymorphism; Health Sciences; Heterogeneity; Hippocampus (Brain); Image; Impairment; Individual; Individual Differences; Inflammatory; Institutes; International; Interview; Knowledge; Link; Lipids; Magnetic Resonance Imaging; Massachusetts; Measures; Medical Genetics; Memory; Methods; Neurocognition; Neurocognitive; Neurologic; New York; Onset of illness; Outcome Measure; Participant; Pathway interactions; Patients; Plasma; Positron; Positron-Emission Tomography; Proteins; Proteomics; Research; Research Personnel; Resource Sharing; Resources; Risk; Sampling; Scientist; Sensitivity and Specificity; Severities; Testing; Texas; Therapeutic Intervention; Universities; amyloid peptide; base; blood-based biomarker; cerebrovascular; clinical Diagnosis; clinical predictors; cognitive ability; cognitive testing; cohort; demented; endophenotype; executive function; experience; genetic analysis; genetic variant; high risk; imaging biomarker; imaging genetics; imaging study; informant; insight; longitudinal analysis; mild cognitive impairment; multidisciplinary; multimodality; neuroimaging; neuroimaging marker; neuropathology; neuropsychiatric symptom; neuropsychiatry; normal aging; pre-clinical; predictive modeling; prospective; public health relevance; rate of change; repository; tau Proteins; tomography; uptake; white matter

 DESCRIPTION (provided by applicant): By age 40 years, individuals with Down syndrome (DS) show the neuropathological changes of Alzheimer's disease (AD) and have a high risk for dementia, but little is known about the biomarkers that may predict clinical onset or reflect disease progression. This study focuses on a longitudinal and multidisciplinary determination of key biomarkers that are likely to define this progression, including levels and rates of change in blood based biomarkers such as -amyloid peptides, protein and lipid profiles, and measures of amyloid and tau concentration in cerebrospinal fluid, neuroimaging-based changes and genetic polymorphisms. Using a neurocognitive battery that we have developed and tested, systematic profiles of longitudinal stability and of decline will allow us to define dementia status, includin Mild Cognitive Impairment in DS (MCI-DS), and characterize progression in clinical status. Previously generated protein, inflammatory and lipid signatures will be examined, as well as amyloid and tau profiles in cerebrospinal fluid (CSF). Imaging biomarkers will include structural MRI components and PET studies of brain amyloid uptake. Analysis of MRI imaging biomarkers will include longitudinal measures of atrophy, white matter abnormalities and intrinsic network connectivity paradigms. Amyloid positron tomography will delineate regional and whole brain uptake of amyloid. Polymorphisms in candidate genes for AD and related biomarkers will be studied as potential modifiers of risk and their relation to beta amyloid, proteomic, lipidomic and imaging biomarkers examined. Relationships among demographic, clinical, blood based and CSF biomarkers, imaging measures, and genetic variants will be examined to develop the most valid indicators of preclinical and early stages of AD. Importantly, the data and the biological samples will be archived and banked to establish a resource to be shared with other scientists. Collectively, our investigators have a combined clinical and research experience involving over 1500 patients (30% demented), over 850 banked blood samples, 500 DNA samples, and 50 imaging studies. Further, team investigators have previous experience with all methods that will be included in this new project. Thus, this application brings together a group of co-investigators with established expertise in studies of DS and makes available a combined cohort of 280 participants.

 描述（由申请人提供）：到 40 岁时，患有唐氏综合症 (DS) 的个体会表现出阿尔茨海默氏病 (AD) 的神经病理学变化，并且具有患痴呆症的高风险，但对于可预测临床发作或痴呆的生物标志物知之甚少。这项研究的重点是对可能定义这种进展的关键生物标志物进行纵向和多学科测定，包括基于血液的生物标志物（如 β-淀粉样肽、蛋白质和脂质）的水平和变化率。使用我们开发和测试的神经认知电池，纵向稳定性和衰退的系统图谱将使我们能够定义痴呆症状态，包括轻度痴呆症。 DS 认知障碍（MCI-DS），以及先前产生的蛋白质、炎症和脂质特征以及淀粉样蛋白和临床状态进展特征。脑脊液 (CSF) 中的 tau 蛋白谱将包括大脑淀粉样蛋白摄取的结构 MRI 成分和 PET 研究，其中包括萎缩、白质异常和淀粉样蛋白正电子断层扫描的纵向测量。将研究 AD 候选基因和相关生物标志物中淀粉样蛋白的区域和全脑摄取，作为风险的潜在修饰因素及其与 β 的关系。淀粉样蛋白、蛋白质组、脂质组和 将检查人口统计学、临床、血液和脑脊液生物标志物、成像测量和遗传变异之间的关系，以开发 AD 临床前和早期阶段的最有效指标。重要的是，数据和生物样本将被存档。总的来说，我们的研究人员拥有涉及 1500 多名患者（30% 患有痴呆症）、超过 850 份储存的血液样本、500 份 DNA 的综合临床和研究经验。此外，团队研究人员以前对将包含在这个新项目中的所有方法都有经验，因此，该应用程序汇集了一组共同​​研究人员。 拥有 DS 研究方面的专业知识，并提供了 280 名参与者的联合队列。