Evaluation of promoter methylation patterns of the 12 frequently mutated genes revealed several significant alterations including hypermethylation of the APC promoter in CRC and AD tissue specimens (p < 0.05; Δβ = 0.27–0.39) (Fig. 3a), hypermethylation of the TP53 promoter in AD (p < 0.001; Δβ = 0.40) and hypomethylation of CTNNB1 (p < 0.05; Δβ between − 0.30 and − 0.45) (Fig. 3a) and SMAD2 (p = 0.024; Δβ = − 0.28) in CRC compared to NAT samples. Here, SMAD2 is linked to Alzheimer disease.