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

NEUROBIOLOGY OF AGING

卷:47

Article

Smith, Adam R.¹  Smith, Rebecca G.¹  Condliffe, Daniel²  Hannon, Eilis¹  Schalkwyk, Leonard³  Mill, Jonathan^1,4  Lunnon, Katie¹ 

[1] Univ Exeter, Sch Med, RILD, Inst Biomed & Clin Sci, Exeter EX4 4QJ, Devon, England

[2] Queen Mary Univ London, Sch Biol & Chem Sci, London, England

[3] Univ Essex, Sch Biol Sci, Wivenhoe Pk, Colchester, Essex, England

[4] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat SGDP Ctr, London, England

关键词: TREM2;    Alzheimer's disease;    Braak stage;    DNA methylation;    Epigenetics;    AD;    Brain;   

DOI  :  10.1016/j.neurobiolaging.2016.07.008

来源: Elsevier

【 摘 要 】

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 hyper-methylation (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. (C) 2016 Elsevier Inc. All rights reserved.

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