Increased DNA methylation near TREM2 is consistently seen in the superior temporal gyrus in Alzheimer’s disease brain

Publication date: Available online 16 July 2016
Source:Neurobiology of Aging
Author(s): Adam Smith, Rebecca G. Smith, Daniel Condliffe, Eilis Hannon, Leonard Schalkwyk, Jonathan Mill, Katie Lunnon
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 AD brain at a CpG site located 289bp upstream of the transcription start site of the TREM2 gene in three independent study cohorts using two different technologies (Illumina Infinium 450K methylation beadchip and pyrosequencing). A meta-analysis across all three cohorts reveals consistent Alzheimer's disease associated hypermethylation (p=3.47E-08). This study highlights that extending genetic studies of TREM2 in Alzheimer's disease to investigate epigenetic changes may nominate additional mechanisms by which disruption to this gene increases risk.



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