UC Irvine AD Translational Center for Disease Model Resources-Spatial Transcriptomics Supplement

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Project Summary/Abstract Neurodegenerative disease mechanisms encompassing Alzheimer’s disease (AD) are complex and have remained largely unknown to date despite the identification of risk factors and genetic mutations associated with the disease. One of the major goals of the UC Irvine MODEL-AD project is to characterize rigorous, reproducible and translatable animal model studies of Alzheimer’s disease (AD), the most common form of neurodegenerative dementia. In this respect, the deep characterization of mouse models of AD using high throughput gene-expression studies at bulk (RNA-seq) and single-cell resolutions (single-nuclei RNA-seq; snRNA-seq) have the potential to unravel novel biology and define drivers of the disease, which is of great therapeutic value. However, current bulk and single-nuclei transcriptomics approaches lack the ability to encode spatial, brain region-specific information, which are crucial to decipher gene-expression changes in the local environment and address long standing questions on how expression of neuronal and glial genes changes during progression of AD-related pathology. The current project represents a major advance in the field by taking a comprehensive approach to data-driven discovery to identify spatial organization of resident neural cells and how they change during the progression of AD. Finally, the project will identify shared transcriptomic signatures between human and mouse model systems in a spatially-resolved manner.