Lardenoije, Roy, Roubroeks, Janou A. Y., Pishva, Ehsan, Leber, Markus, Wagner, Holger, Iatrou, Artemis, Smith, Adam R., Smith, Rebecca G., Eijssen, Lars M. T., Kleineidam, Luca, Kawalia, Amit, Hoffmann, Per, Luck, Tobias ORCID: 0000-0001-7551-4397, Riedel-Heller, Steffi, Jessen, Frank, Maier, Wolfgang, Wagner, Michael ORCID: 0000-0003-2589-6440, Hurlemann, Rene ORCID: 0000-0003-2628-565X, Kenis, Gunter, Ali, Muhammad, del Sol, Antonio, Mastroeni, Diego, Delvaux, Elaine, Coleman, Paul D., Mill, Jonathan ORCID: 0000-0003-1115-3224, Rutten, Bart P. F., Lunnon, Katie, Ramirez, Alfredo ORCID: 0000-0003-4991-763X and van den Hove, Daniel L. A. (2019). Alzheimer's disease-associated (hydroxy)methylomic changes in the brain and blood. Clin. Epigenetics, 11 (1). LONDON: BMC. ISSN 1868-7083

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Abstract

Background Late-onset Alzheimer's disease (AD) is a complex multifactorial affliction, the pathogenesis of which is thought to involve gene-environment interactions that might be captured in the epigenome. The present study investigated epigenome-wide patterns of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC), as well as the abundance of unmodified cytosine (UC), in relation to AD. Results We identified epigenetic differences in AD patients (n = 45) as compared to age-matched controls (n = 35) in the middle temporal gyrus, pertaining to genomic regions close to or overlapping with genes such as OXT (- 3.76% 5mC, p(Sidak) = 1.07E-06), CHRNB1 (+ 1.46% 5hmC, p(Sidak) = 4.01E-04), RHBDF2 (- 3.45% UC, p(Sidak) = 4.85E-06), and C3 (- 1.20% UC, p(Sidak) = 1.57E-03). In parallel, in an independent cohort, we compared the blood methylome of converters to AD dementia (n = 54) and non-converters (n = 42), at a preclinical stage. DNA methylation in the same region of the OXT promoter as found in the brain was found to be associated with subsequent conversion to AD dementia in the blood of elderly, non-demented individuals (+ 3.43% 5mC, p(Sidak) = 7.14E-04). Conclusions The implication of genome-wide significant differential methylation of OXT, encoding oxytocin, in two independent cohorts indicates it is a promising target for future studies on early biomarkers and novel therapeutic strategies in AD.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lardenoije, RoyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roubroeks, Janou A. Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pishva, EhsanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leber, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iatrou, ArtemisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, Adam R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, Rebecca G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eijssen, Lars M. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleineidam, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kawalia, AmitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luck, TobiasUNSPECIFIEDorcid.org/0000-0001-7551-4397UNSPECIFIED
Riedel-Heller, SteffiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Hurlemann, ReneUNSPECIFIEDorcid.org/0000-0003-2628-565XUNSPECIFIED
Kenis, GunterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ali, MuhammadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
del Sol, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mastroeni, DiegoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delvaux, ElaineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coleman, Paul D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mill, JonathanUNSPECIFIEDorcid.org/0000-0003-1115-3224UNSPECIFIED
Rutten, Bart P. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lunnon, KatieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
van den Hove, Daniel L. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-127022
DOI: 10.1186/s13148-019-0755-5
Journal or Publication Title: Clin. Epigenetics
Volume: 11
Number: 1
Date: 2019
Publisher: BMC
Place of Publication: LONDON
ISSN: 1868-7083
Language: English
Faculty: Faculty of Management, Economy and Social Sciences
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; DNA METHYLATION; GLOBAL CHANGES; 5-HYDROXYMETHYLCYTOSINE; OXYTOCIN; DEMENTIA; HYDROXYMETHYLATION; HEALTH; ROLES; COGNITIONMultiple languages
Oncology; Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12702

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