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. 2016 Nov;47:35-40.
doi: 10.1016/j.neurobiolaging.2016.07.008. Epub 2016 Jul 16.

Increased DNA Methylation Near TREM2 Is Consistently Seen in the Superior Temporal Gyrus in Alzheimer's Disease Brain

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Free PMC article

Increased DNA Methylation Near TREM2 Is Consistently Seen in the Superior Temporal Gyrus in Alzheimer's Disease Brain

Adam R Smith et al. Neurobiol Aging. .
Free PMC article

Abstract

Although mutations within the TREM2 gene have been robustly associated with Alzheimer's disease, it is not known whether alterations in the regulation of this gene are also involved in pathogenesis. Here, we present data demonstrating increased DNA methylation in the superior temporal gyrus in Alzheimer's disease brain at a CpG site located 289 bp upstream of the transcription start site of the TREM2 gene in 3 independent study cohorts using 2 different technologies (Illumina Infinium 450K methylation beadchip and pyrosequencing). A meta-analysis across all 3 cohorts reveals consistent AD-associated hypermethylation (p = 3.47E-08). This study highlights that extending genetic studies of TREM2 in AD to investigate epigenetic changes may nominate additional mechanisms by which disruption to this gene increases risk.

Keywords: AD; Alzheimer's disease; Braak stage; Brain; DNA methylation; Epigenetics; TREM2.

Figures

Figure 1
Figure 1
DNA methylation is consistently increased in AD samples compared to controls in the STG at chr6:41,131,213. (A) Adjusted methylation levels of cg25748868 in the STG in non-demented controls (Braak stage 0–II) and AD (Braak stage V–VI) samples from three cohorts. In all three cohorts DNA methylation at this loci is increased in AD cases relative to controls. (B) Forest plot of meta-analysis of effect size of cg25748868 across the three cohorts. Key: * = P<0.05, ** = P<0.01, *** = P<0.005
Figure 1
Figure 1
DNA methylation is consistently increased in AD samples compared to controls in the STG at chr6:41,131,213. (A) Adjusted methylation levels of cg25748868 in the STG in non-demented controls (Braak stage 0–II) and AD (Braak stage V–VI) samples from three cohorts. In all three cohorts DNA methylation at this loci is increased in AD cases relative to controls. (B) Forest plot of meta-analysis of effect size of cg25748868 across the three cohorts. Key: * = P<0.05, ** = P<0.01, *** = P<0.005

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