Estrogen and the Aging Primate Brain

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Activity on this trans-institutional collaborative has extended our survey of estrogenic effects on markers of neuronal aging in relation to cognitive outcomes in rhesus monkeys. In a recently published study of this sort, Crimins et al. (2019) used serial section electron microscopy methods pioneered by the Morrison group at UC Davis to quantify the synaptic compartmental representation of phosphorylated tau (at serine 214; pS214-tau) in layer III of the dorsolateral prefrontal cortex in an ovariectomized model of menopause and estrogen replacement in young and aged monkeys. Levels of immunogold pS214-tau labeling were decreased with aging in all synaptic compartments examined. These effects, however, were independent of cognitive and estrogen status. Although phosphorylated tau has typically been of interest in the context of age-related neuropathology, taken together our findings in monkeys point a potential physiological role for pS214-tau in supporting synaptic health. Studies of this sort fill a critical gap in understanding the basis of synaptic vulnerabilities that are increasingly recognized as a key seed event in neurodegenerative disease.