Abstract (30 lines): existing cerebrospinal fluid (CSF) and neuroimaging measures of amyloid SS, TAU and neurodegeneration (a, t, n) serve as useful diagnostic biomarkers for alzheimer's disease (ad), however there remains an urgent, unmet need for blood based biomarkers in ad. First, multi-omic studies discovered many perturbed biological pathways in ad, however, systematic studies for biomarkers that capture these diverse biological facets of ad are limited. Second, ad is a heterogeneous disorder but biomarkers that can distinguish the biological subtypes of ad are lacking. Third, core ad neuropathology often CO-exists with other neuropathologies such as vascular disease (v). These CO-morbidities and CO-pathologies need to be considered in biomarker discovery. Fourth, existing biomarker studies are heavily focused on non-hispanic whites (NHW). Similar studies in underrepresented populations (URP) are needed. This U19, bringing together >40 experts across 13 institutions, aims to bridge these knowledge gaps for discovery and validation of centrally-linked longitudinal peripheral biomarkers of ad (clear-ad) in multi-ethnic populations. Clear-ad U19 is based on the premise that ad is a complex disorder in which many biological pathways are disrupted due to multi-omic perturbations, which can be detected in brain and reflected in blood, i.e. centrally-linked peripheral molecular signatures (clpms). The specific aims of clear-ad U19 are: 1) to discover clpms of the complex and heterogeneous ad pathophysiology and its CO-pathologies. 2) to identify longitudinal clpms that detect and predict dynamic neuroimaging, fluid biomarker, and clinical changes across ad spectrum. 3) to characterize differences and similarities in clpms profiles across NHW, african american (AA) and latino american (LA) participants to uncover biomarker patterns in multi-ethnic groups. 4) to make these vast resources available to the scientific community to amplify and accelerate its impact. In this U19 managed by the administrative core, we will leverage NIH-funded adni, mcsa and adrc cohorts of >3,700 multi-ethnic participants to generate >20,000 multi-omics measures (omics core) that will be processed and integrated with >48,000 harmonized ad cognitive, neuroimaging and fluid endophenotypes (analytic core). Using these data, we will identify brain region and cell-type specific clpms, which reflect biological subtypes of ad and disease stage (project 1). We will discover longitudinal changes in clpms that predict cognitive and a/t/n/v progression (project 2). We will define longitudinal cognitive and a/t/n/v changes and clpms in URP that are either conserved with NHW or population-specific (project 3). This U19 will a) identify the next generation of ad biomarkers with mechanistic insights; b) establish a precision medicine approach for rigorous multi-omics biomarker discovery and validation in ad; c) discover molecules that can serve as biomarkers and therapeutic targets; d) enhance biomarker research in trial-ready multi-ethnic populations; and e) generate and share a vast and harmonized resource of endophenotype and multi-omics data in NIH-funded cohorts.
University Of WashingtonThe UW subcontract for the U19 includes support for the leadership role of Dr. Mukherjee (team leader for the cognitive harmonization team), and for most of the…
$102,420
University Of FloridaThe University of Florida will provide annually for five years (2022-2027), samples and data collected from African American and Latin American participants…
$30,702
Trustees Of Indiana UniversityThe IU site of the Omics Core (Core 2) will be responsible for the conducting RNA-seq for the biospecimen collected in Project 2 and Project 3 (IU cohort).…
Trustees Of Indiana UniversityDr. Nho will lead the Analytic Core with co-leader, Dr. Li at the Mayo Clinic, and will assist the PI and MPIs of the proposed U19 project with 1)…
$595,982
The Trustees Of The University Of PennsylvaniaUniversity of Pennsylvania will participate in the prime grant awarded to Mayo Clinic. The Penn team will work with the Mayo Clinic team and the Indiana…
$39,812
Duke UniversityDr. Kaddurah-Daouk will bring her vast experience in metabolomic studies of Alzheimer’s Disease and neuropsychiatric diseases for the implementation of this…
$31,335
The Trustees Of The University Of PennsylvaniaUniversity of Pennsylvania will participate in the prime grant awarded to Mayo Clinic. The Penn team will work with the Mayo Clinic team and the Indiana…
$36,562
Sage BionetworksSage Bionetworks (Sage) has built a set of expertise and services over the past decade that has enabled responsible data sharing in over 50 consortia. Our…
$136,403
Trustees Of Indiana UniversityThe IU site of the Omics Core (Core 2) will be responsible for the conducting RNA-seq for the biospecimen collected in Project 2 and Project 3 (IU cohort).…
$822,071
The Washington UniversityCruchaga laboratory at Washington University will provide brain, blood DNA and/or RNA from Hispanics and African American AD cases and controls Cruchaga lab…
$104,850
University Of WashingtonUniversity of Washington will participate in the prime grant awarded to Mayo Clinic. Analytic Core: Dr. Mukerjee will lead the Analytic Core with co-leader, Dr.…
$85,006
University Of FloridaThe Perrin Laboratory supports the Alzheimer’s Disease Neuroimaging Initiative Neuropathology Core (ADNI NPC) and the Charles F. and Joanne Knight…
$34,113
Duke UniversityDuke University will participate in the prime grant awarded to Mayo Clinic. Analytic Core: Dr. Nho will lead the Analytic Core with co-leader, Dr. Li at the…
$394,236
The Trustees Of The University Of PennsylvaniaThe Penn team will work with the Mayo Clinic team and the Indiana University (IU) team on developing and applying computational methods for identifying…
$40,625
The Washington UniversityThe Perrin Laboratory supports the Alzheimer’s Disease Neuroimaging Initiative Neuropathology Core (ADNI NPC) and the Charles F. and Joanne Knight…
$104,395
Sage BionetworksSage Bionetworks will participate in the prime grant awarded to Mayo Clinic. Analytic Core: Dr. Nho will lead the Analytic Core with co-leader, Dr. Li at the…
$139,188
Trustees Of Indiana UniversityIndiana University will participate in the prime grant awarded to Mayo Clinic. Analytic Core: Dr. Nho will lead the Analytic Core with co-leader, Dr. Li at…
$1,155,348
Trustees Of Indiana UniversityIndiana University – (IU) will participate in the prime grant awarded to Mayo Clinic. Analytic Core: Dr. Nho will lead the Analytic Core with…
$608,145
Trustees Of Indiana UniversityIndiana University will participate in the prime grant awarded to Mayo Clinic. Analytic Core: Dr. Nho will lead the Analytic Core with co-leader, Dr. Li at…
$711,586
Trustees Of Indiana UniversityIndiana University – (IU) will participate in the prime grant awarded to Mayo Clinic. Analytic Core: Dr. Nho will lead the Analytic Core with…
$608,145
Trustees Of Indiana UniversityIndiana University – (IU) will participate in the prime grant awarded to Mayo Clinic. Project 2: Drs. Saykin and Nho will co-lead the Project 2…
$711,586
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Quick answers
Who received award U19AG074879?
U19AG074879 was awarded to Mayo Clinic Jacksonville (A Nonprofit Corporation) by National Institute on Aging (National Institutes of Health) on March 15, 2023.
Mayo Clinic Jacksonville (A Nonprofit Corporation) UEI GKPBCFV1QMM3 Part of Mayo Clinic
National Institute on Aging
National Institutes of Health, Department of Health and Human Services