Life expectancy of individuals with Down Syndrome (DS) is currently 60 years. From age 40 they have an increased risk of dementia and almost all of them have histopathological features of Alzheimer’s desease (AD) in their brains. Also, it is known that the ε4 allele of the APOE gene and the R47H variant of TREM2 increase the risk of AD. DS is also associated with a group of clinical manifestations of accelerated aging. DNA methylation-based biomarkers of ageing (epigenetic clocks) can be assessed by different models. It is known that DNA methylation age (DNAm) has a positive correlation with chronological age in disomic individuals while DS subjects exhibit an age acceleration effect in blood and brain. Here, we analyzed the acceleration in DNAm age in adults with DS using the Horvath’s model and its correlation with cognitive impairment.
We determined the DNAm age of 7 participants with DS in peripheral blood leukocytes. Median age was 47 years. Variants in APOE and TREM2 were analyzed by RFLP-PCR.
Five participants exhibited the 3/3 genotype in APOE and two of them the 3/4. The R47H variant in TREM2 was not observed. Five participants showed a significant biological age acceleration and one participant’s DNAm age was similar to his chronological age. Of note, one participant showed a deceleration in the DNAm age. We did not find a trend towards a greater presence of the risk allele ε4 or cognitive impairment in participants with a significant DNAm age acceleration.