Single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease

Qi Wang, Jerry Antone, Eric Alsop, Rebecca Reiman, Cory Funk, Jaroslav Bendl, Joel T. Dudley, Winnie S. Liang, Timothy L. Karr, Panos Roussos, David A. Bennett, Philip L. Jager, Geidy E. Serrano, Thomas G. Beach, Kendall Keuren-Jensen, Diego Mastroeni, Eric M. Reiman and Benjamin P. Readhead ()
Additional contact information
Qi Wang: Arizona State University
Jerry Antone: The Translational Genomics Research Institute
Eric Alsop: The Translational Genomics Research Institute
Rebecca Reiman: The Translational Genomics Research Institute
Cory Funk: Institute for Systems Biology
Jaroslav Bendl: Icahn School of Medicine at Mount Sinai
Joel T. Dudley: Arizona State University
Winnie S. Liang: The Translational Genomics Research Institute
Timothy L. Karr: Arizona State University
Panos Roussos: Icahn School of Medicine at Mount Sinai
David A. Bennett: Rush University Medical Center
Philip L. Jager: Columbia University Irving Medical Center
Geidy E. Serrano: Banner Sun Health Research Institute
Thomas G. Beach: Banner Sun Health Research Institute
Kendall Keuren-Jensen: The Translational Genomics Research Institute
Diego Mastroeni: Arizona State University
Eric M. Reiman: Banner Alzheimer’s Institute
Benjamin P. Readhead: Arizona State University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract The emergence of single nucleus RNA sequencing (snRNA-seq) offers to revolutionize the study of Alzheimer’s disease (AD). Integration with complementary multiomics data such as genetics, proteomics and clinical data provides powerful opportunities to link cell subpopulations and molecular networks with a broader disease-relevant context. We report snRNA-seq profiles from superior frontal gyrus samples from 101 well characterized subjects from the Banner Brain and Body Donation Program in combination with whole genome sequences. We report findings that link common AD risk variants with CR1 expression in oligodendrocytes as well as alterations in hematological parameters. We observed an AD-associated CD83(+) microglial subtype with unique molecular networks and which is associated with immunoglobulin IgG4 production in the transverse colon. Our major observations were replicated in two additional, independent snRNA-seq data sets. These findings illustrate the power of multi-tissue molecular profiling to contextualize snRNA-seq brain transcriptomics and reveal disease biology.

Date: 2024
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DOI: 10.1038/s41467-024-49790-0

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