1. Single cell transcriptomes and multiscale networks from persons with and without Alzheimer's disease.
- Author
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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, and Readhead BP
- Subjects
- Humans, Male, Female, Aged, Microglia metabolism, Aged, 80 and over, Oligodendroglia metabolism, Middle Aged, Immunoglobulin G metabolism, Gene Regulatory Networks, Sequence Analysis, RNA, Brain metabolism, Brain pathology, Gene Expression Profiling, Alzheimer Disease genetics, Alzheimer Disease metabolism, Transcriptome, Single-Cell Analysis
- 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., (© 2024. The Author(s).)
- Published
- 2024
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