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Bridging the gap: Multi-omics profiling of brain tissue in Alzheimer’s disease and older controls in multi-ethnic populations

Affiliations
  • 1Mayo Clinic Florida, Jacksonville, Florida, USA.
  • 2Sage Bionetworks, Seattle, Washington, USA.
  • 3Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
  • 4Emory University School of Medicine, Atlanta, Georgia, USA.
  • 5Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • 6Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • 7Columbia University Irving Medical Center, New York, New York, USA.
  • 8New York Genome Center, New York, New York, USA.
  • 9University of Illinois Chicago, Chicago, Illinois, USA.
  • 10The Glen Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas, San Antonio, Texas, USA.
  • 11University of Florida, Gainesville, Florida, USA.
  • 12Center for Neurodegenerative Disease Brain Bank at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • 13Banner Sun Health Research Institute, Sun City, Arizona, USA.

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August 31, 2024

Abstract

INTRODUCTION

Multi-omics studies in Alzheimer’s disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD.

METHODS

To bridge this gap, Accelerating Medicines Partnership in Alzheimer’s Disease (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors.

RESULTS

We generated multi-omics data and curated and harmonized phenotypic data from BA (n = 306), LA (n = 326), or BA and LA (n = 4) brain donors plus non-Hispanic White (n = 252) and other (n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures.

DISCUSSION

The inclusion of traditionally underrepresented groups in multi-omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD.

HIGHLIGHTS

Accelerating Medicines Partnership in Alzheimer’s Disease Diversity Initiative led brain tissue profiling in multi-ethnic populations. Brain multi-omics data is generated from Black American, Latin American, and non-Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled.

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