Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Lardenoije, Roy UNSPECIFIED UNSPECIFIED UNSPECIFIED Roubroeks, Janou A. Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pishva, Ehsan UNSPECIFIED UNSPECIFIED UNSPECIFIED Leber, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Iatrou, Artemis UNSPECIFIED UNSPECIFIED UNSPECIFIED Smith, Adam R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Smith, Rebecca G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eijssen, Lars M. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleineidam, Luca UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawalia, Amit UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Per UNSPECIFIED UNSPECIFIED UNSPECIFIED Luck, Tobias UNSPECIFIED orcid.org/0000-0001-7551-4397 UNSPECIFIED Riedel-Heller, Steffi UNSPECIFIED UNSPECIFIED UNSPECIFIED Jessen, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Maier, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Michael UNSPECIFIED orcid.org/0000-0003-2589-6440 UNSPECIFIED Hurlemann, Rene UNSPECIFIED orcid.org/0000-0003-2628-565X UNSPECIFIED Kenis, Gunter UNSPECIFIED UNSPECIFIED UNSPECIFIED Ali, Muhammad UNSPECIFIED UNSPECIFIED UNSPECIFIED del Sol, Antonio UNSPECIFIED UNSPECIFIED UNSPECIFIED Mastroeni, Diego UNSPECIFIED UNSPECIFIED UNSPECIFIED Delvaux, Elaine UNSPECIFIED UNSPECIFIED UNSPECIFIED Coleman, Paul D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mill, Jonathan UNSPECIFIED orcid.org/0000-0003-1115-3224 UNSPECIFIED Rutten, Bart P. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lunnon, Katie UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramirez, Alfredo UNSPECIFIED orcid.org/0000-0003-4991-763X UNSPECIFIED van den Hove, Daniel L. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language GENOME-WIDE ASSOCIATION; DNA METHYLATION; GLOBAL CHANGES; 5-HYDROXYMETHYLCYTOSINE; OXYTOCIN; DEMENTIA; HYDROXYMETHYLATION; HEALTH; ROLES; COGNITION Multiple languages Oncology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12702