Accelerated epigenetic aging in adults with Down’s syndrome in the Argentine population

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Alzheimer’s dementia. 2021; Dec 17 2: e058593. doi: 10.1002 / alz.058593.


Context: The life expectancy of people with Down’s Syndrome (DS) is currently 60 years. From the age of 40, they have an increased risk of dementia and almost all have histopathological features of Alzheimer’s disease (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. Biomarkers of aging based on DNA methylation (epigenetic clocks) can be assessed by different models. It is known that the age of DNA methylation (mDNA) correlates positively with chronological age in disomic individuals, while DS subjects exhibit an age-accelerating effect in blood and blood. brain.

METHOD: We determined the mDNA age of a cohort of seven participants with chromosome 21 trisomy (confirmed by G-band karyotyping). The median age was 49 years old. Their cognitive state was assessed by clinical and neuropsychological assessments. The risk variants of AD in APOE and TREM2 were analyzed by RFLP-PCR. DNA age was assessed in peripheral blood leukocytes using the Illumina 850K platform. We used Horvath’s epigenetic clock, based on the mDNA levels of 353 specific CpG sites.

RESULT: Five participants had the ε3 / ε3 genotype in APOE and two of them the ε3 / ε4 genotype. We did not observe the R47H risk variant in TREM2 in this group. Five participants showed significant biological acceleration in age, and a participant’s mDNA age was similar to their chronological age. Of note, one participant showed a deceleration in the age of mDNA. This participant also had multiple myeloma. The DNA methylation profile of multiple myeloma cells is known to differ from that of normal plasma cells. On the other hand, we did not find a trend for a greater presence of the ε4 risk allele or cognitive impairment in participants with significant mDNA acceleration.

Conclusion: The majority of the participants presented an acceleration of their biological age, but this fact was not correlated with a greater presence of the allele at risk ε4 or cognitive impairment. This is the first dataset on DNA methylation ages from a cohort of people with Down syndrome in Latin America.

PMID: 34971139 | DOI: 10.1002 / alz.058593

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