An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene

NEUROBIOLOGY OF AGING

卷:95

Article

Roubroeks, Janou A. Y.¹  Smith, Adam R.¹  Smith, Rebecca G.¹  Pishva, Ehsan^1,2  Ibrahim, Zina^3,4  Sattlecker, Martina³  Hannon, Eilis J.¹  Kloszewska, Iwona⁵  Mecocci, Patrizia⁶  Soininen, Hilkka^7,8  Tsolaki, Magda⁹  Vellas, Bruno¹⁰  Wahlund, Lars-Olof¹¹  Aarsland, Dag^12,13  Proitsi, Petroula^12,14,15  Hodges, Angela¹²  Lovestone, Simon^16,17  Newhouse, Stephen J.^12,14,15  Dobson, Richard J. B.^3,4  Mill, Jonathan¹  van den Hove, Daniel L. A.^2,18  Lunnon, Katie¹ 

[1] Univ Exeter, Coll Med & Hlth, Exeter, Devon, England

[2] Maastricht Univ, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci MHeNS, Maastricht, Netherlands

[3] Kings Coll London, Inst Psychiat Psychol & Neurosci IOPPN, Dept Biostat & Hlth Informat, London, England

[4] UCL, Farr Inst Hlth Informat Res, London, England

[5] Med Univ Lodz, Lodz, Poland

[6] Univ Perugia, Inst Gerontol & Geriatr, Perugia, Italy

[7] Univ Eastern Finland, Inst Clin Med, Neurol, Kuopio, Finland

[8] Kuopio Univ Hosp, Neuroctr, Neurol, Kuopio, Finland

[9] Aristotle Univ Thessaloniki, Dept Neurol 1, Memory & Dementia Unit, Thessaloniki, Greece

[10] Univ Toulouse, INSERM U 558, Toulouse, France

[11] Karolinska Inst, Sect Clin Geriatr, NVS Dept, Stockholm, Sweden

[12] Kings Coll London, Inst Psychiat Psychol & Neurosci, Kings Hlth Partners Ctr Neurodegenerat Res, London, England

[13] Stavanger Univ Hosp, Ctr Age Related Dis, Stavanger, Norway

[14] Kings Coll London, NIHR Biomed Res Ctr Mental Hlth South London & Ma, London, England

[15] Kings Coll London, Inst Psychiat, London, England

[16] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England

[17] Janssen Cilag UK, Wycombe, England

[18] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany

关键词: Alzheimer's disease (AD);    Biomarker;    Blood;    DNA methylation;    HOXB6;    Mild cognitive impairment (MCI);   

DOI  :  10.1016/j.neurobiolaging.2020.06.023

来源: Elsevier

【 摘 要 】

A growing number of epigenome-wide association studies have demonstrated a role for DNA methylation in the brain in Alzheimer's disease. With the aim of exploring peripheral biomarker potential, we have examined DNA methylation patterns in whole blood collected from 284 individuals in the Add-NeuroMed study, which included 89 nondemented controls, 86 patients with Alzheimer's disease, and 109 individuals with mild cognitive impairment, including 38 individuals who progressed to Alzheimer's disease within 1 year. We identified significant differentially methylated regions, including 12 adjacent hypermethylated probes in the HOXB6 gene in Alzheimer's disease, which we validated using pyrosequencing. Using weighted gene correlation network analysis, we identified comethylated modules of genes that were associated with key variables such as APOE genotype and diagnosis. In summary, this study represents the first large-scale epigenome-wide association study of Alzheimer's disease and mild cognitive impairment using blood. We highlight the differences in various loci and pathways in early disease, suggesting that these patterns relate to cognitive decline at an early stage. (C) 2020 The Authors. Published by Elsevier Inc.

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