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. De Jager; Geidy E. Serrano; Thomas G. Beach; Kendall Van Keuren-Jensen; Diego Mastroeni; Eric M. Reiman; Benjamin P. Readhead

doi:10.1038/s41467-024-49790-0

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. De Jager, Geidy E. Serrano, Thomas G. Beach, Kendall Van Keuren-Jensen, Diego Mastroeni, Eric M. Reiman, Benjamin P. Readhead

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3 Scopus citations

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.

Original language	English (US)
Article number	5815
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-49790-0
State	Published - Dec 2024

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Wang, Q., Antone, J., Alsop, E., Reiman, R., Funk, C., Bendl, J., Dudley, J. T., Liang, W. S., Karr, T. L., Roussos, P., Bennett, D. A., De Jager, P. L., Serrano, G. E., Beach, T. G., Van Keuren-Jensen, K., Mastroeni, D., Reiman, E. M., & Readhead, B. P. (2024). Single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease. Nature communications, 15(1), Article 5815. https://doi.org/10.1038/s41467-024-49790-0

Wang, Q, Antone, J, Alsop, E, Reiman, R, Funk, C, Bendl, J, Dudley, JT, Liang, WS, Karr, TL, Roussos, P, Bennett, DA, De Jager, PL, Serrano, GE, Beach, TG, Van Keuren-Jensen, K, Mastroeni, D, Reiman, EM & Readhead, BP 2024, 'Single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease', Nature communications, vol. 15, no. 1, 5815. https://doi.org/10.1038/s41467-024-49790-0

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abstract = "The emergence of single nucleus RNA sequencing (snRNA-seq) offers to revolutionize the study of Alzheimer{\textquoteright}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.",

author = "Qi Wang and Jerry Antone and Eric Alsop and Rebecca Reiman and Cory Funk and Jaroslav Bendl and Dudley, {Joel T.} and Liang, {Winnie S.} and Karr, {Timothy L.} and Panos Roussos and Bennett, {David A.} and {De Jager}, {Philip L.} and Serrano, {Geidy E.} and Beach, {Thomas G.} and {Van Keuren-Jensen}, Kendall and Diego Mastroeni and Reiman, {Eric M.} and Readhead, {Benjamin P.}",

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AU - Dudley, Joel T.

AU - Liang, Winnie S.

AU - Karr, Timothy L.

AU - Roussos, Panos

AU - Bennett, David A.

AU - De Jager, Philip L.

AU - Serrano, Geidy E.

AU - Beach, Thomas G.

AU - Van Keuren-Jensen, Kendall

AU - Mastroeni, Diego

AU - Reiman, Eric M.

AU - Readhead, Benjamin P.

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

Abstract

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