Increased blood COASY DNA methylation levels a potential biomarker for early pathology of Alzheimer’s disease

Abstract

Early diagnosis of dementia including Alzheimer's disease (AD) is an urgent medical and welfare issue. However, to date, no simple biometrics have been available. We reported that blood DNA methylation levels of the COASY gene, which encodes coenzyme A synthase, were increased in individuals with AD and amnestic mild cognitive impairment (aMCI). The present study sought to replicate these findings with larger numbers of samples. Another objective was to clarify whether COASY methylation is associated with neurodegeneration through a comparison of AD, AD with cardiovascular disease (CVD), and vascular dementia (VaD). We measured blood COASY methylation levels in normal controls (ncs) (n = 200), and individuals with aMCI (n = 22), AD (n = 151), and VaD (n = 21). Compared with NCs, they were significantly higher in individuals with aMCI and AD. Further, they were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them. These findings suggest that COASY methylation levels may be related to neurodegeneration in AD.

Recent Evidence in Epigenomics and Proteomics Biomarkers for Early and Minimally Invasive Diagnosis of Alzheimer’s and Parkinson’s Diseases

“…They detected significant hypermethylation in AD and amnestic MCI (aMCI) vs. healthy controls (HC) and proposed COASY methylation as a diagnostic biomarker due to its high sensitivity and specificity (>96%) [ 93 ]. Although these studies were performed in a small cohort (30 AD patients, 28 aMCI patients, and 30 HC), this group validated these results this year in a larger cohort (AD (151), vascular dementia (VaD) (21), MCI (22), HC (200)) [ 100 ]. Moreover, this recent study has also pointed out that COASY methylation levels were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them [ 100 ].…”

“…Although these studies were performed in a small cohort (30 AD patients, 28 aMCI patients, and 30 HC), this group validated these results this year in a larger cohort (AD (151), vascular dementia (VaD) (21), MCI (22), HC (200)) [ 100 ]. Moreover, this recent study has also pointed out that COASY methylation levels were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them [ 100 ]. However, as far as we know, these results have not been subsequently corroborated by other authors.…”

Blood DNA Methylation Levels in the WNT5A Gene Promoter Region: A Potential Biomarker for Agitation in Subjects with Dementia

“…The participants for the study to compare DNA methylation levels between with and without agitation were 108 patients who had visited Aira-no-mori Hospital (Aira-gun, Kagoshima Prefecture), been diagnosed with dementia and were under treatment. Among them were 63 subjects whose data was used in our previously published research [ 18 ]. The breakdown of the present subjects was 67 with AD, 27 with vascular dementia (VaD), and 6 with dementia with Lewy bodies (DLB).…”

“…Genomic DNA was extracted from peripheral blood cells using QIAamp DNA Blood Midi Kit (Qiagen). According to the same procedure as used previously, APOE genotypes (rs429358 and rs7412) were determined by allelic discrimination on an Applied Biosystems 7300 real-time PCR System (Thermo Fisher Scientific) [ 18 ].…”

“…According to the same method as in our previous research, DNA methylation levels in the WNT5A gene promoter region were measured by MS-HRM analysis [ 18 ]. Brief details are given below.…”