Alzheimer's Disease Research Center

阿尔茨海默病研究中心

基本信息

批准号：
10613998
负责人：
Mary Sano
金额：
$ 345.84万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10613998
关键词：
Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Amyloid Area Autopsy Awareness Big Data Big Data Methods Biological Biological Markers Biological Process Biology Blood Blood Vessels Body Fluids Brain Brain region Characteristics Clinical Clinical Course of Disease Clinical Trials Design Cognitive deficits Collection Communities Complex Computerized Medical Record Data Data Science Data Set Data Sources Dedications Dementia Detection Development Discipline Disease Disease model Economics Environment Epigenetic Process Excision Exclusion Exhibits Faculty Faculty Recruitment Failure Fostering Functional Imaging Genetic Genomics Goals Growth Health Heterogeneity Human Image Impaired cognition Individual Informatics Infrastructure Institution Intervention Knowledge Leadership Life Location Medical center Methods Mission Nerve Degeneration Pain Participant Pathogenicity Pathology Patients Phenotype Plasma Population Population Heterogeneity Preparation Probability Proteomics Race Recording of previous events Research Research Personnel Resources Risk Sampling Science Scientific Inquiry Secure Specimen Supercomputing Symptoms System Tauopathies Technology Therapeutic Time Tissues Training Translational Research Traumatic Brain Injury Underrepresented Minority Underrepresented Populations United States Department of Veterans Affairs biological heterogeneity clinical heterogeneity clinically relevant cohort computerized tools convict demented design disease heterogeneity education research exosome experience genetic analysis genome wide association study improved induced pluripotent stem cell innovation institutional capacity interdisciplinary collaboration medical schools microbiome molecular imaging molecular phenotype multidisciplinary multiple omics neuropathology new technology novel outreach patient engagement pharmacologic prevent recruit research clinical testing scientific computing skills stressor structural imaging success therapeutic development

项目摘要

Mount Sinai ADRC (Sano): OVERALL – Research Summary Alzheimer's disease (AD) is a major health threat to the nation and the world causing great human pain and economic loss. While some advances have been made in detection and raising awareness, finding treatments has remained unsuccessful in spite of decades of research. To date, efforts have focused on defining the disease by a narrow characterization of end-stage pathology, using restrictive samples and technologies that systematically exclude the diversity of the disease. This approach has led to multiple failures, resulting in scant progress on the therapeutic front. With this backdrop, the Mount Sinai Alzheimer's Disease Research Center (MSADRC), with its history of success in therapeutic development dedicates itself anew to identify and develop effective approaches to treating AD. Co-located in Manhattan on the Mount Sinai campus and in the Bronx at the James J Peters Veterans Administration Medical Center, we bring the strength of two premiere institutions to the mission of finding a treatment for AD. This application builds on these institutional strengths including systems- based approaches to scientific inquiry, using the computational tools to mine big data and our established expertise in recruiting diverse populations. We propose as our theme “Understanding disease heterogeneity to optimize therapeutic approaches to treat and cure Alzheimer's disease” as it aligns our strengths with the implementation areas and milestones of the National Alzheimer's Project Act (NAPA). We propose 7 cores (Administrative, Clinical, Biomarker, Genetics, Neuropathology, Data, and Outreach) and a Research Education Component, all of which have outstanding leadership reflecting newly recruited faculty as well investigators with established histories at the MSADRC. Using the collaborative efforts of the Clinical and Outreach Core, enhanced by novel methods of patient engagement through the electronic medical records at both locations, we propose to expand and maintain a cohort of 450 diverse individuals, 40% of whom will be from under-represented minorities, all receiving annual clinical evaluations, genetic analysis, and blood biomarker collection. The Genetics Core will collect genetics data on all, generate GWAS, and will obtain plasma samples for established biomarkers and proteomics on this diverse cohort. Our new Biomarker Core, supported by new philanthropy and existing research efforts will obtain structural and functional imaging on all patients, and molecular phenotyping with CSF biomarkers or molecular imaging on at least 50% of the cohort, capturing its full diversity. The Neuropathology Core, expanding collection beyond brain to other relevant tissues and body fluids obtained at autopsy, will allow the preparation of relevant brain regions for unbiased systematic sampling (stereology) and autopsy-derived specimens for iPS, multiomics, microbiome, and exosome studies. The Data Core, enhanced by the addition of the Senior Associate Dean for Scientific Computing and Data Science as Core Co-Leader, will expand the capacity to integrate and share the Core's resources to facilitate interdisciplinary collaborations and create an environment that fosters innovative approaches to finding treatments and cures.

西奈山ADRC（Sano）：总体 - 研究摘要阿尔茨海默氏病（AD）是对国家和世界的主要健康威胁，造成了巨大的人类痛苦和经济损失。虽然在发现和提高意识方面已取得了一些进步，但要寻找治疗方法尽管研究了数十年，但仍未成功。迄今为止，努力重点是定义疾病通过对终阶段病理的狭窄表征，使用限制性样本和技术系统地排除疾病的多样性。这种方法导致多次失败，导致很少在治疗方面的进展。在这种背景下，西奈山阿尔茨海默氏病研究中心（MSADRC），其在理论发展中的成功历史将自己献身于识别和发展有效治疗广告的方法。在西奈山校园和布朗克斯的曼哈顿共同位置詹姆斯·J·彼得斯退伍军人管理局医疗中心，我们将两个首映机构的实力带到找到AD治疗的使命。该应用程序以这些机构优势为基础，包括系统 - 基于科学探究的方法，使用计算工具来挖掘大数据和我们已建立的招募潜水员人群的专业知识。我们建议我们的主题“了解疾病异质性优化治疗和治愈阿尔茨海默氏病的方法《国家阿尔茨海默氏症计划法》（NAPA）的实施区域和里程碑。我们提出了7个核心（行政，临床，生物标志物，遗传学，神经病理学，数据和外展）以及研究教育组成部分，所有这些都有出色的领导在MSADRC建立的历史。利用临床和外展核心的协作努力，增强了通过两个位置通过电子病历的新型患者参与方法，我们建议扩大和维护450名潜水员的队列，其中40％来自代表性不足的少数民族，所有接受年度临床评估，遗传分析和血液生物标志物收集。遗传学核心将收集所有遗传学数据，生成GWAS，并将获得已建立生物标志物的血浆样本和该潜水队的蛋白质组学。我们的新生物标志物核心，得到新的慈善和现有研究的支持努力将对所有患者进行结构和功能成像，并使用CSF生物标志物进行分子表型或在至少50％的队列上进行分子成像，捕获其全部多样性。神经病理学核心，将大脑以外的收集扩展到尸检时获得的其他相关时间和体液，将允许为无偏系统采样（立体学）和尸检的相关大脑区域的准备 IPS，多组学，微生物组和外泌体研究的标本。数据核心通过添加而增强作为核心共同领导者科学计算和数据科学的高级副院长将使能力扩大到集成并共享核心资源以促进跨学科合作并创建环境这促进了创新的方法来寻找治疗方法和治疗方法。