KBASE2: Korean Brain Aging Study, Longitudinal Endophenotypes and Systems Biology

KBASE2：韩国大脑衰老研究、纵向内表型和系统生物学

• 批准号: 10199190
• 负责人: Dong Young Lee
• 金额: $ 240.48万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10199190
• 关键词: Address; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Amyloid; Angiography; Asians; Automobile Driving; Back; Biological Markers; Blood; Blood Vessels; Brain; California; Clinical; Clinical Data; Clinical assessments; Cognition; Cognitive; Collaborations; Collection; Complement; Data; Data Collection; Data Set; Data Storage and Retrieval; Dementia; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Early Diagnosis; Elements; Enrollment; Ethnic group; European; Follow-Up Studies; Functional Magnetic Resonance Imaging; Genes; Genetic; Genetic Risk; Genetic Transcription; Genetic Variation; Genetic study; Genome; Genomics; Goals; Image; Indiana; Institutes; International; Korea; Koreans; Laboratories; Machine Learning; Magnetic Resonance Imaging; Medical Genetics; Memory; Methods; Molecular; Multiomic Data; Nerve Degeneration; Network-based; Participant; Pathology; Pathway Analysis; Pathway interactions; Pennsylvania; Phenotype; Population; Positron-Emission Tomography; Prevention; Process; Prospective cohort study; Public Health; Reporting; Research; Resources; Rest; Risk; Sampling; Science; Site; Specimen; Structure; Systems Biology; Translations; Universities; aging brain; base; cerebrovascular; cohort; comparative; computerized data processing; data harmonization; data sharing; design; drug development; endophenotype; fluorodeoxyglucose positron emission tomography; functional genomics; genetic analysis; genetic variant; genomic data; heterogenous data; imaging biomarker; insight; lifestyle data; longitudinal analysis; member; mild cognitive impairment; multi-ethnic; multidisciplinary; multimodal data; multimodality; multiple omics; neuroimaging; neuroimaging marker; novel diagnostics; novel strategies; polygenic risk score; precision medicine; prevent; prognostic; programs; progression marker; prospective; protective allele; risk variant; sample collection; specific biomarkers; tau Proteins; therapeutic development; therapeutic target; transcriptome sequencing; transcriptomics; whole genome; working group

Project Summary/Abstract The Korean Brain Aging Study for the Early Diagnosis and Prediction of AD (KBASE) is a comprehensive prospective cohort study launched at Seoul National University (SNU) in 2014 using a similar design and methods as the North American Alzheimer’s Disease Neuroimaging Initiative (ADNI). The KBASE cohort consists of well-characterized participants including cognitively normal (CN) controls with a wide age range (20 to 90 years), mild cognitive impairment (MCI) and AD dementia (AD). A unique aspect of KBASE is the systematic longitudinal collection of comprehensive clinical, cognitive and lifestyle data, multimodal neuroimaging (MRI/MRA, DTI, rsfMRI, amyloid, tau and FDG PET), and bio-specimens in Korea for the first five years (“KBASE1”). Some KBASE data have been analyzed and reported but much of the extensive KBASE data set and samples await comprehensive analysis. The proposed project (“KBASE2”) represents a collaboration between the NIA Alzheimer’s Disease Sequencing Project (ADSP) and partners, Indiana University (ADNI Genetics Core, Indiana NIA-designated ADRC, and IU Network Science Institute), the KBASE team at SNU in Korea, University of Southern California (USC), and the University of Pennsylvania. Over 1000 whole genome sequences (WGS) of Korean participants will be contributed to the ADSP, and the extensive ADSP multi-ethnic data set will be analyzed. WGS data will be harmonized by the NIA Genetics and Genomics Center for AD (GCAD) and shared via the NIA Genetics of AD Data Storage Site (NIAGADS). The Laboratory of Neuroimaging (LONI) at USC will support sharing of MRI and PET and related endophenotypes, as it does for ADNI. KBASE2 will continue longitudinal data and sample collection and provide high throughput WGS and RNA-Seq as well as data harmonization and sharing (Aim 1), perform intensive brain network-based analyses of longitudinal amyloid, tau, neurodegeneration and vascular (A/T/N/V) imaging biomarkers in relation to clinical data (Aim 2), employ integrative systems biology and functional genomics methods to analyze multi-omics data for association with A/T/N/V biomarkers for AD, and provide new insight into AD biomarker-related dysregulated gene modules and pathways (Aim 3). The overarching concepts driving this multidisciplinary international collaborative project are that 1) development of precision medicine for AD and related disorders (ADRD) requires systematic multi-modal biomarker collection in diverse cohorts during early at-risk stages of disease to identify robust diagnostic, prognostic and therapeutic targets and 2) sophisticated analytic strategies that address the complexity of multi- layer multimodal data and heterogeneous and diverse participant cohorts are essential. We hypothesize that integrative longitudinal analysis of genetic and -omics networks with structural and functional brain networks will yield new diagnostic and treatment-relevant insights related to A/T/N/V and other aging related pathways. Results of this collaboration and data sharing will facilitate translation of ADSP findings for therapeutic development in support of the National Alzheimer's Project Act goal of prevention and treatment of AD by 2025.

项目摘要/摘要 韩国大脑老化研究的早期诊断和预测（KBase）是一个全面的 预期队列研究于2014年在首尔国立大学（SNU）启动 方法作为北美阿尔茨海默氏病神经影像学倡议（ADNI）。 KBase队列 由特征良好的参与者组成，包括具有广泛年龄范围的认知正常（CN）对照（20 到90年），轻度认知障碍（MCI）和AD痴呆症（AD）。 KBase的一个独特方面是 全面的临床，认知和生活方式数据的系统纵向收集，多模式 神经影像学（MRI/MRA，DTI，RSFMRI，淀粉样蛋白，TAU和FDG PET）和韩国的生物规定在前五个 年（“ kbase1”）。一些KBASE数据已经进行了分析和报告，但大量广泛的KBase数据 设定和样品等待全面分析。拟议的项目（“ KBASE2”）代表合作 在NIA阿尔茨海默氏病测序项目（ADSP）与印第安纳大学（ADNI）的合作伙伴之间 遗传学核心，印第安纳州NIA指定的ADRC和IU网络科学学院），SNU的KBASE团队 韩国，南加州大学（USC）和宾夕法尼亚大学。超过1000个全基因组 韩国参与者的序列（WGS）将为ADSP和广泛的ADSP贡献 数据集将进行分析。 WGS数据将由NIA遗传学和AD基因组学中心协调 （GCAD）并通过AD数据存储位点（Niagads）的NIA遗传学共享。神经成像实验室 （LONI）在南加州大学（USC）将支持MRI和PET及相关的内表型的共享，就像对ADNI一样。 kbase2 将继续纵向数据和样本收集，并提供高吞吐量WGS和RNA-seq以及 数据协调和共享（AIM 1），对纵向淀粉样蛋白进行密集的基于大脑网络的分析， tau，神经退行性和血管（A/T/N/V）成像生物标志物与临床数据相关（AIM 2），采用 集成系统的生物学和功能基因组学方法分析多词数据以与 A/T/N/V生物标志物用于AD，并提供有关与AD生物标志物相关的基因模块的新见解和 途径（目标3）。驱动这个多学科国际协作项目的总体概念是 1）开发用于AD和相关疾病的精密医学（ADRD）需要系统的多模式 在疾病早期风险阶段，潜水员队列中的生物标志物收集以识别可靠的诊断， 预后和治疗靶标以及2）解决多数复杂性的复杂分析策略 层多模式数据和异质和潜水员的参与者队列至关重要。我们假设这一点 具有结构和功能性脑网络的遗传和摩学网络的综合纵向分析将 产生与A/T/N/V以及其他与衰老相关的途径有关的新诊断和相关的见解。 这种合作和数据共享的结果将有助于翻译ADSP调查结果 支持《国家阿尔茨海默氏症的项目法案》的发展目标，以预防和治疗AD到2025年。