Alzheimer’s disease-associated (hydroxy)methylomic changes in the brain and blood
Posted on 2019-11-28 - 04:59
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, pŠidák = 1.07E−06), CHRNB1 (+ 1.46% 5hmC, pŠidák = 4.01E−04), RHBDF2 (− 3.45% UC, pŠidák = 4.85E−06), and C3 (− 1.20% UC, pŠidák = 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, pŠidák = 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.
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Lardenoije, Roy; Roubroeks, Janou; Pishva, Ehsan; Leber, Markus; Wagner, Holger; Iatrou, Artemis; et al. (2019). Alzheimer’s disease-associated (hydroxy)methylomic changes in the brain and blood. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4762448.v1
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AUTHORS (29)
RL
Roy Lardenoije
JR
Janou Roubroeks
EP
Ehsan Pishva
ML
Markus Leber
HW
Holger Wagner
AI
Artemis Iatrou
AS
Adam Smith
RS
Rebecca Smith
LE
Lars Eijssen
LK
Luca Kleineidam
AK
Amit Kawalia
PH
Per Hoffmann
TL
Tobias Luck
SR
Steffi Riedel-Heller
FJ
Frank Jessen
WM
Wolfgang Maier
MW
Michael Wagner
RH
René Hurlemann
GK
Gunter Kenis
MA
Muhammad Ali