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DNA methylation of imprint control regions associated with Alzheimer's disease

Cevik, et. al. Clin Epigenetics 16:58 (2024)    

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7 May 2024: Using WGBS and the recently identified human imprintome (Jima et al., 2022), we provide the first evidence that DNA methylation in 120 candidate imprint control regions (ICRs) varies markedly in the brains of people with Alzheimer's disease (AD) versus that in controls (Cevik et al., 2024).

Eighty-one and 27 ICRs were differentially methylated in non Hispanic blacks (NHBs) and non Hispanic whites (NHWs), respectively. Interestingly, only two ICRs were in common to both populations, those that are proximal to a known imprinted gene, MEST/MESTIT1 (ICR_481) and the inflammasome gene, NLRP1 (ICR_987). The three fold increased in the frequency of ICRs with methylation changes in NHBs with AD compared to that in NHWs with AD may contribute to the higher prevalence of AD in NHBs (Alzheimer's Association, 2023).

These findings are also consistent with the developmental origins of health and disease (DOHaD) hypothesis. It postulates that an increased susceptibility to adult-onset chronic diseases, such as AD, frequently have their origins in early development (Gauvrit et al., 2022), and support the findings that AD is characterized by changes in the brain that likely start decades before the clinical symptoms appear (Beason-Held et al., 2013). Thus, alteration in ICR methylation may serve as an early detection tool of AD risk that is essential for slowing the progression of this disease.

In conclusion, these findings indicate that early developmental alterations in the DNA methylation of regions regulating genomic imprinting contribute to AD risk, and that this epigenetic risk differs significantly between NHBs and NHWs.