Increased DNA methylation near TREM2 is consistently seen in the superior temporal gyrus in Alzheimer's disease brain.
Neurobiology of Aging
© 2016 Elsevier Inc. All rights reserved.
Reason for embargo
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.
This work was funded by a grant from BRACE (Bristol Research into Alzheimer's and Care of the Elderly) and the Alzheimer's Society (grant number AS-PG-14-038) to Katie Lunnon and NIH grant R01 AG036039 and an Equipment Grant from Alzheimer's Research UK to Jonathan Mill. The authors thank Carolyn Sloan for technical support and Istvan Bodi and Andrew King for neuropathological diagnosis of cases. The authors also thank the Oxford Project to Investigate Memory and Ageing (OPTIMA), the National Institute for Health (NIHR), Biomedical Research Unit in Dementia in the South London and Maudsley NHS Foundation Trust (SLaM), Brains for Dementia Research (Alzheimer Brain Bank UK) and the donors and families who made this research possible. The Oxford Brain Bank is supported in part by the National Institute for Health Research (NIHR), Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University Of Oxford. Brain banking and neuropathology assessments for the Mount Sinai cohort was supported by NIH grants AG02219, AG05138, and MH064673 and the Department of Veterans AffairsVISN3 MIRECC.
This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.
Vol. 47, pp. 35 - 40
Place of publication