U01AG072177

KBASE2: Korean Brain Aging Study, Longitudinal Endophenotypes and Systems Biology - 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). It will 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). It will 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.

Trustees Of Indiana University

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Indianapolis, Indiana 462022207 United States

Single Zip Code

Limited Competition: Analysis of Data from NIA's Alzheimer's Disease Sequencing Project Follow-Up Study (U01) (PAR-17-214)

Amendment Since initial award the total obligations have increased 366% from $2,404,788 to $11,202,386.