The Aging Brain: Age- and Sex-Related Changes in Glial Cells within the Entorhinal Cortex of Rhesus Macaques

As the global population of people over 65 increases, so does the risk for developing dementia such as Alzheimer’s Disease. This neurodegenerative disease leads to severe cognitive decline and memory deficits as a result of dysregulation in neurons. While the symptoms of Alzheimer's are well-characterized, the mechanisms contributing to this disease pathology are not fully understood. In this study, I used rhesus macaques as models for age-related cognitive decline based on their similarities in brain structure with humans. The RNA sequencing data in this study came from four different types of glial cells in the entorhinal cortex of the brain: oligodendrocytes, microglia, astrocytes, and oligodendrocyte precursor cells (OPCs). I observed that glial cell classes exhibit sex differences in cell composition, with males generally displaying greater changes in cell composition with age than females. A greater number of differentially expressed genes were upregulated with age than were downregulated. Multiple genes in every glial cell class were directly related to neuronal function and maintenance. Generally, genes upregulated with age in these cells were related to synaptic signaling and neuron development. These findings showcase changes in glial cells that could potentially be linked to cellular pathways involved in Alzheimer’s pathogenesis. With a more robust understanding of how specific genes in these types of cells change with age, it could be possible to improve early disease detection methods.