Alzheimer's Disease Research Center

阿尔茨海默病研究中心

基本信息

批准号：
10406865
负责人：
Mary Sano
金额：
$ 304.2万
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/10406865
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 Dementia Detection Development Discipline Disease Disease model Economics Ensure Environment Epigenetic Process Excision Exhibits Faculty Faculty Recruitment Failure Fostering Functional Imaging Genetic Genomics Goals Growth Health Heterogeneity Human Image Impaired cognition Individual Informatics Infrastructure Institutes Institution Intervention Knowledge Leadership Life Location Medical center Methods Mission Nerve Degeneration Pain Participant Pathogenicity Pathology Patients Pharmacology Phenotype Plasma Population Population Heterogeneity Preparation Proteomics 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 Ursidae Family base biological heterogeneity clinical biomarkers clinical heterogeneity clinically relevant cohort computerized tools convict 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 prevent recruit research clinical testing scientific computing skills stressor 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（萨诺）：总体 – 研究摘要阿尔茨海默病（AD）是对国家和世界的主要健康威胁，给人类带来巨大痛苦和虽然在检测和提高认识方面取得了一些进展，但寻找治疗方法。尽管进行了数十年的研究，但仍未取得成功，人们的努力主要集中在对该疾病的定义上。通过对终末期病理学的狭义表征，使用限制性样本和技术系统地排除疾病的多样性，这种方法导致了多次失败，导致很少。在此背景下，西奈山阿尔茨海默病研究中心在治疗方面取得了进展。（MSADRC）在治疗开发方面拥有成功的历史，再次致力于识别和开发治疗 AD 的有效方法位于曼哈顿西奈山校区和布朗克斯校区。詹姆斯·J·彼得斯退伍军人管理局医疗中心，我们将两家一流机构的实力带到了寻找 AD 治疗方法的使命该应用程序建立在这些机构优势的基础上，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建立的我们建议我们的主题是“了解疾病异质性”。优化治疗方法来治疗和治愈阿尔茨海默病”，因为它将我们的优势与国家阿尔茨海默病项目法案 (NAPA) 的实施领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）和研究教育组成部分，所有这些都具有杰出的领导力，反映了新招募的教员以及研究人员通过临床和外展核心的协作努力，在 MSADRC 建立了历史。通过两个地点的电子病历与患者互动的新颖方法，我们建议扩大并维持一个由 450 名不同人士组成的群体，其中 40% 来自代表性不足的少数族裔，所有这些都将接受年度临床评估、遗传分析和血液生物标志物收集。收集所有人的遗传学数据，生成 GWAS，并获取已建立生物标志物的血浆样本，我们的新生物标志物核心，得到新慈善事业和现有研究的支持。将获得所有患者的结构和功能成像成果，以及脑脊液生物标志物的分子表型分析或对至少 50% 的队列进行分子成像，捕获其全部多样性的神经病理学核心，尸检时获得的脑外其他相关组织和体液的收集，将允许为无偏见的系统采样（体视学）和尸检衍生的相关大脑区域进行准备用于 iPS、多组学、微生物组和外泌体研究的样本，通过添加增强的数据核心。科学计算和数据科学高级副院长作为核心联合领导者，将扩大能力整合和共享核心资源，促进跨学科合作，创造环境这促进了寻找治疗方法和治愈方法的创新方法。