Blood methylomic signatures of presymptomatic dementia in elderly subjects with type 2 diabetes mellitus

NEUROBIOLOGY OF AGING

卷:36

Article

Lunnon, Katie¹  Smith, Rebecca G.²  Cooper, Itzik³  Greenbaum, Lior^3,4  Mill, Jonathan^1,2  Beeri, Michal Schnaider^3,5 

[1] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England

[2] Kings Coll London, Inst Psychiat, Genet & Dev Psychiat Ctr, MRC Social, London WC2R 2LS, England

[3] Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel

[4] Sheba Med Ctr, Dept Neurol, Ramat Gan, Israel

[5] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

关键词: DNA methylation;    Biomarker;    Epigenetics;    Alzheimer's disease (AD);    Blood;    Type 2 diabetes;    Dementia;   

DOI  :  10.1016/j.neurobiolaging.2014.12.023

来源: Elsevier

【 摘 要 】

Due to an aging population, the incidence of dementia is steadily rising. The ability to identify early markers in blood, which appear before the onset of clinical symptoms is of considerable interest to allow early intervention, particularly in high risk groups such as those with type 2 diabetes. Here, we present a longitudinal study of genome-wide DNA methylation in whole blood from 18 elderly individuals with type 2 diabetes who developed presymptomatic dementia within an 18-month period following baseline assessment and 18 age-, sex-, and education-matched controls who maintained normal cognitive function. We identified a significant overlap in methylomic differences between groups at baseline and follow-up, with 8 CpG sites being consistently differentially methylated above our nominal significance threshold before symptoms at baseline and at 18 months follow up, after a diagnosis of presymptomatic dementia. Finally, we report a significant overlap between DNA methylation differences identified in converters, only after they develop symptoms of dementia, with differences at the same loci in blood samples from patients with clinically diagnosed Alzheimer's disease compared with unaffected control subjects. (C) 2015 Elsevier Inc. All rights reserved.

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