The main goal of the Ginsberg laboratory is to understand the molecular and cellular substrates that regulate the selective vulnerability of neurons to degeneration. A multidisciplinary approach of state-of-the-art ‘omics approaches, including microaspiration of select neuronal types through laser capture microdissection and single-population RNA-sequencing along with protein–protein interaction network-based approaches combined with immunohistochemical and cell biological techniques is utilized as part of the experimental design. Particular emphasis is placed on analyzing the interactomes of individual neuronal populations as a means of understanding the complex cascade of cellular events that occurs under pathologic conditions such as aging, the Alzheimer’s disease (AD) spectrum, and Down syndrome (DS), as well as employing relevant animal and cellular models of neurodegenerative disorders.