Technological advances in single cell and spatial genomics have created the opportunity to create comprehensive atlases of the entire brain that map the cellular complexity of functional architecture across species including human.  These atlases and their classification of cell types provide a foundation for understanding brain function, brain diseases and creating new tools for genetic access to specific cell types.  This talk will focus on three main topics:  First, describing the latest efforts in human brain cell atlasing, and illustrating the use of comparative strategies to understand what makes human brain distinctive.  Second, demonstrating how these tools and knowledge can be used to understand specific cellular vulnerabilities and affected molecular pathways in Alzheimer’s disease.  Finally, illustrating how these genomics-based atlases can be used to identify short enhancer elements that can confer cell type-selective gene expression that can be used in viral vectors for basic research or potentially even therapeutically relevant gene therapy applications.