Nov 30, 2019

Alzheimer's disease-associated (hydroxy)methylomic changes in the brain and blood

Clinical Epigenetics
Roy LardenoijeDaniel L A van den Hove

Abstract

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. 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). The implication of genome-wide significant differential methylat...Continue Reading

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Mentioned in this Paper

Biological Markers
Study
Patterns
Pathogenesis
Genome
Genes
Brain
Gene-Environment Interaction
Cytosine
DNA Methylation

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