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 leads to neurodegeneration. Until now most of the 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.

The authors have declared no competing interest.

The Arizona Study of Aging and Neurodegenerative Disorders Brain and Body Donation Program at Banner Sun Health Research Institute, Sun City, Arizona has been supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson Disease and Related Disorders), the National Institute on Aging (P30 AG019610 and P30AG072980, Arizona Alzheimer Disease Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson Disease Consortium) and the Michael J. Fox Foundation for Parkinson Research.

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The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of WCG for studies involving humans. Study Number 1132516.

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