Using single nucleus RNA sequencing (snRNA-seq) on brain samples from 101 people, NOMIS researcher Eric Reiman and colleagues found links between common Alzheimer’s disease (AD) risk genes and changes in specific brain cells and blood properties. They also identified a unique type of microglial cell associated with AD and which is associated with immune responses in the gut. Their research demonstrates that multi-tissue molecular profiling is a powerful tool for understanding Alzheimer’s disease. Their findings were published in Nature Communications.
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.
Read the Nature Communications publication: Single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease
