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

基本信息

批准号：
9895314
负责人：
IRA T. LOTT
金额：
$ 35.55万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9895314
关键词：
Activities of Daily Living Adult Affect Age Alzheimer&apos s Disease Alzheimer&apos s disease risk Alzheimer’s disease biomarker 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 Structure Testing Texas Therapeutic Intervention Universities amyloid peptide base blood-based biomarker cerebrovascular clinical Diagnosis clinical predictors cognitive ability cognitive testing cohort demented dementia risk early detection biomarkers 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 rate of change repository tau Proteins tomography uptake white matter

项目摘要

ABSTRACT 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, including 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 proposal brings together a group of co-investigators with established expertise in studies of DS and makes available a combined cohort of 280 participants.

抽象的到40岁时，患有唐氏综合症（DS）的个体显示了阿尔茨海默氏症的神经病理学变化疾病（AD），痴呆症的风险很高，但对可能预测的生物标志物知之甚少临床发作或反映疾病进展。这项研究重点是纵向和多学科确定可能定义此进展的关键生物标志物，包括变化的水平和速率在基于血液的生物标志物中，例如淀粉样蛋白和脂质谱，淀粉样蛋白和淀粉样蛋白的测量脑脊液中的tau浓度，基于神经影像学的变化和遗传多态性。使用我们已经开发和测试的神经认知电池，纵向稳定性和下降将使我们能够定义痴呆状态，包括DS（MCI-DS）中的轻度认知障碍和表征临床状况的进展。以前产生的蛋白质，炎症和脂质特征将在脑脊液（CSF）中检查，以及淀粉样蛋白和TAU谱。成像生物标志物将包括脑淀粉样蛋白摄取的结构MRI成分和PET研究。 MRI成像生物标志物的分析将包括萎缩，白质异常和内在网络连接的纵向测量范式。淀粉样蛋白正电子断层扫描将描绘淀粉样蛋白的区域和整个大脑吸收。 AD和相关生物标志物的候选基因中的多态性将被研究为潜在的风险修饰符以及它们与β-淀粉样蛋白组，蛋白质组学，脂质组和成像生物标志物的关系。关系在人口统计学，临床，基于血液和CSF生物标志物中，成像测量和遗传变异将会进行检查以制定AD的临床前和早期阶段的最有效指标。重要的是，数据和生物样品将进行存档和存储，以建立与其他科学家共享的资源。总的来说，我们的研究人员拥有涉及1500多名患者的临床和研究经验（30％痴呆），超过850种储存的血液样本，500个DNA样品和50个成像研究。此外，团队调查人员以前具有所有方法，这些方法将包括在这个新项目中。那，这个提案汇集了一群共同投资者，在DS研究方面具有既定专业知识，并使可提供280名参与者的组合队列。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Support vector machine learning and diffusion-derived structural networks predict amyloid quantity and cognition in adults with Down's syndrome.

DOI：
10.1016/j.neurobiolaging.2022.02.013
发表时间：
2022-07
期刊：
NEUROBIOLOGY OF AGING
影响因子：
4.2
作者：
Brown, Stephanie S. G.;Mak, Elijah;Clare, Isabel;Grigorova, Monika;Beresford-Webb, Jessica;Walpert, Madeline;Jones, Elizabeth;Hong, Young T.;Fryer, Tim D.;Coles, Jonathan P.;Aigbirhio, Franklin I.;Tudorascu, Dana;Cohen, Annie;Christian, Bradley T.;Handen, Benjamin L.;Klunk, William E.;Menon, David K.;Nestor, Peter J.;Holland, Anthony J.;Zaman, Shahid H.
通讯作者：
Zaman, Shahid H.

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