Characterization of Isolated Human Astrocytes from Aging Brain

Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance, and responding to injury and repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading to imbalances in the brain's internal milieu that eventually impact neuronal function and lead to neurodegeneration. Until now, most evidence of astrocytic dysfunction in aging has come from experiments done with whole tissue homogenates, astrocytes collected by laser capture, or cell cultures derived from animal models or cell lines. In this study, we used postmortem-derived whole cells sorted with anti-GFAP antibodies to compare the unbiased, whole-transcriptomes of human astrocytes from control, older non-impaired individuals and subjects with different neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (ADD), and progressive supranuclear palsy (PSP). We found hundreds of dysregulated genes between disease and control astrocytes. In addition, we identified numerous genes shared between these common neurodegenerative disorders that are similarly dysregulated; in particular, UBC a gene for ubiquitin, which is a protein integral to cellular homeostasis and critically important in regulating function and outcomes of proteins under cellular stress, was upregulated in PSP, PD, and ADD when compared to control.