Blood DNA methylation levels of the oxytocin promoter predict conversion from mild cognitive impairment to dementia in females within a clinical cohort of cognitive complaints

Abstract

AbstractRecent studies have highlighted the role of oxytocin (OXT) in Alzheimer’s disease (AD) dementia and demonstrated its potential as a therapeutic target to reverse cognitive impairment and mitigate AD pathology. Epigenetic dysregulation ofOXThas been identified in brain tissue from AD patients, and DNA methylation levels of the exact same locus in the blood of healthy aged individuals have shown predictive biomarker value for conversion to AD. Building on these insights, we investigated the DNA methylation status of theOXTpromoter in blood in a prospective cohort of consecutive patients from the BioBank Alzheimer Center Limburg (BBACL). This cohort included males and females suffering from subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. Our findings revealed that DNA methylation levels of theOXTpromoter at baseline predict the conversion from MCI to dementia in female participants. In addition to discovering differences in theOXTpromoter related to sex, we also observed alterations associated with aging, alcohol consumption, and smoking. Overall, our findings underscore the implications ofOXTand its DNA methylation changes in blood within the context of dementia.