A blood-based panel of DNA methylation markers improves diagnosis accuracy of Alzheimer’s disease

Abstract Background: This work investigated the diagnostic accuracy of a blood-based DNA methylation marker panel as a non-invasive tool to identify Alzheimer's disease (AD) patients. Methods: Blood DNA methylation levels at 46 CpG sites (21 genes selected after a comprehensive literature search) were measured in 80 patients with probable AD dementia and 100 age- and sex-matched controls by bisulfite pyrosequencing. Plasma pTau181 levels were determined by Simoa technology. Multivariate logistic regression analysis was performed to explore the optimal model to discriminate AD patients from controls. Results: A panel including DNA methylation levels at NXN (>0.81), TREML2 (<0.27) and HOXA3(>0.91) genes and plasma pTau181 (>1.82 pg/mL) significantly improved (AUC=0.94; P value < 0.01) the diagnostic performance of a single pTau181-based model, adjusted for age, sex and APOEɛ4 genotype. After sex-stratified analysis, HOXA3DNA methylation levels showed consistently associated to AD. Conclusions: These results highlight the potential translational value of blood-based DNA methylation biomarkers for the diagnosis of AD.