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

ABSTRACT: Due to an increasingly aging population, the incidence of dementias such as Alzheimer’s disease are steadily rising, with recent estimates predicting >115million dementia sufferers by 2050. 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 longitudinal genome-wide DNA methylation data comparing 18 elderly individuals with T2D who developed pre-symptomatic dementia within an 18 month period following baseline assessment to 18 age, sex and education matched controls who maintained normal cognitive function. We identified a highly significant overlap in the effect size of the top-ranked methylation sites at baseline and follow-up, and identified 8 robust loci, some of which have been previously related to neurodegenerative processes, which were consistently differentially methylated prior to symptoms at baseline, and at 18 month follow up, when a diagnosis of pre-symptomatic dementia had been provided. Finally we show a significant overlap in the effect size of the top-ranked methylation sites in converters, only after they develop symptoms of pre-symptomatic dementia, with changes at the same loci in blood samples from patients with clinically-diagnosed Alzheimer’s disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE62003 | GEO | 2015/02/28

SECONDARY ACCESSION(S): PRJNA262917

REPOSITORIES: GEO

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