[¹¹C]PS13 PET shows that age is positively correlated with constitutively expressed cyclooxygenase-1 in the brain

Cyclooxygenase-1 (COX-1), an essential enzyme in the synthesis of pro-inflammatory prostanoids from arachidonic acid, is widely expressed in the brain, primarily in microglia. Previous studies from our laboratory found that the novel positron emission tomography (PET) radioligand [¹¹C]PS13 has excellent in vivo selectivity for constitutively expressed COX-1 in human brain. This study sought to further evaluate the effects of age and sex on levels of constitutive COX-1 expression in the brains of 56 healthy volunteers. COX-1 density in the brain measured by [¹¹C]PS13 PET showed a significant positive correlation with age in the whole brain, as well as in regions with the highest COX-1 expression, such as the hippocampus, lateral occipital cortex, and pericentral cortex. No significant sex differences were observed in any regions. Consistent findings were observed regardless of partial volume correction (PVC), while overall statistical significance was enhanced with PVC. In conclusion, the present study found that constitutive COX-1 binding in the brain, which is associated with microglial density, increased with age with no significant sex differences. The physiological roles of COX-1 in these regions and its potential contributions to the aging process remain largely unknown, and further investigation is warranted. Clinical trial registration information: NCT03324646; NCT04396873 in ClinicalTrials.gov.