Single-cell, multi-region profiling of the macaque brain across the lifespan
Brain aging is a complex process with profound health and societal consequences. However, the molecular and cellular pathways that govern its temporal progression -- along with cell type-, region-, and sex-specific heterogeneity -- remain poorly defined. Here, we present a transcriptomic atlas of 5.3 million cells from 582 samples spanning 11 brain regions of 55 rhesus macaques (29 female, 26 male), aged 5 months (early life) to 21 years (late adulthood). We annotate 12 major cell classes and 226 subclusters, including region-specific subtypes of excitatory and inhibitory neurons, astrocytes, and ependymal cells. We identify a vulnerable excitatory neuron population in the superficial cortical lamina that is less abundant later in life, along with subtle, region-specific, age-associated compositional differences in subpopulations of microglia and oligodendrocytes, whose detection required single cell resolution. Finally, we chart convergent and divergent age-associated molecular signatures -- some sex-specific -- across brain regions and cell types. This work provides a temporal, regional, and sex-stratified atlas of the aging primate brain, offering insights into cell type-specific vulnerabilities and regional heterogeneity with translational human relevance.