Objective Aberrant promoter methylation of multiple genes is associated with various diseases, including Alzheimer’s disease (AD), however, the relationship between disrupted-in-schizophrenia-1 (DISC1) promoter methylation and the progress of AD is unclear.Methods The methylation levels of the DISC1 promoter were measured in 51 AD patients and 63 controls using bisulfite pyrosequencing assay. Blood biochemical indicators were detected using standard methods.Results DISC1 promoter methylation was significantly higher in AD patients than in controls (P=0.002). Moreover, Both apolipoprotein A (ApoA) and Lipoprotein A (Lp(a)) are significantly correlated with the DISC1 CpG3 methylation. DISC1 methylation is positively correlated with blood ApoA in female (P=0.003). DISC1 methylation is positively correlated with blood Lp(a) in male (P<0.000 1). The area under curve (AUC) of DISC1 promoter methylation is 0.726 (95% CI: 0.626-0.827), the sensitivity is 0.560 and specificity is 0.869.Conclusion The results of the present study demonstrated that elevated DISC1 promoter methylation was associated with AD risk in males, and it may be a potential biomarker for the diagnosis of AD.