Blood methylomic signatures of pre-symptomatic dementia in elderly subjects with Type 2 Diabetes Mellitus

摘要

Due to an aging population, the incidence of dementia is steadily rising. The ability to identify early markers in blood, which appear before the onset of clinical symptoms is of considerable interest to allow early intervention, particularly in “high risk” groups such as those with Type 2 Diabetes (T2D). Here we present a longitudinal study of genome-wide DNA methylation in whole blood from 18 elderly individuals with T2D who developed pre-symptomatic dementia within an 18 month period following baseline assessment and 18 age, sex and education matched controls who maintained normal cognitive function. We identified a significant overlap in methylomic differences between groups at baseline and follow-up, with ten CpG sites, several in the vicinity of loci previously implicated in neurodegenerative processes, being consistently differentially methylated above our nominal significance threshold prior to symptoms at baseline and at 18 month follow up, after a diagnosis of pre-symptomatic dementia. Finally we report a significant overlap between DNA methylation differences identified in converters, only after they develop symptoms of dementia, with differences at the same loci in blood samples from patients with clinically-diagnosed Alzheimer’s disease compared to unaffected controls.