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Neurobiol Aging. 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.

Author information

1
Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD, University of Exeter, Devon, UK.
2
School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.
3
School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, UK.
4
Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD, University of Exeter, Devon, UK; Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
5
Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD, University of Exeter, Devon, UK. Electronic address: k.lunnon@exeter.ac.uk.

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

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