N6-methyladenine-modified DNA was decreased in Alzheimer’s disease patients

Abstract

BACKGROUND In recent years, the prevalence of Alzheimer’s disease (AD) has increased, which places a great burden on society and families and creates considerable challengesfor medical services. N6-methyladenine (m6A) deoxyribonucleic acid (DNA)adenine methylation is a novel biomarker and is abundant in the brain, but lesscommon in AD. We support to analyze the relationship between DNA m6A andcognition in patients with AD and normal controls (NCs) in China.AIMTo analyze the relationship between the novel m6A DNA and cognition inpatients with AD and NCs in China.METHODSA total of 179 AD patients (mean age 71.60 ± 9.89 years; males: 91; females: 88) and147 NCs (mean age 69.59 ± 11.22 years; males: 77; females: 70) who were age and sex-matched were included in our study. All subjects underwent neuropsychologicalscale assessment and magnetic resonance imaging examination. ApolipoproteinE (APOE) genotypes were measured through agarose gel electrophoresis.Global m6A levels were evaluated by a MethylFlash m6A DNA MethylationELISA Kit (colorimetric). Global m6A levels in total DNA from ten AD patientswith 18F-AV-45 (florbetapir) positron emission tomography (PET) positivity andten NCs with PET negativity were analyzed by dot blotting to determine theresults.RESULTSOur ELISA results showed that the global m6A DNA levels in peripheral bloodwere different between patients with AD and NCs (P = 0.002; < 0.05). And ten ADpatients who were PET positive and ten NCs who were PET negative also showedthe same results through dot blotting. There were significant differences betweenthe two groups, which indicated that the leukocyte m6A DNA levels weredifferent (P = 0.005; < 0.05). The m6A level was approximately 8.33% lower in ADpatients than in NCs (mean 0.011 ± 0.006 vs 0.012 ± 0.005). A significant correlationwas found between the Montreal Cognitive Assessment score and the peripheralblood m6A level in the tested population (r = 0.143, P = 0.01; < 0.05). However, norelationship was found with APOE ε4 (P = 0.633, > 0.05). Further studies shouldbe performed to validate these findings.CONCLUSIONOur results show that reduced global m6A DNA methylation levels aresignificantly lower in AD patients than in NCs by approximately 8.33% in China