The aim of the present study was to (1) investigate the relationship between late-onset Alzheimer's disease (AD) and DNA methylation levels in six of the top seven AD-associated genes identified through a meta-analysis of recent genome wide association studies, APOE, BIN1, PICALM, CR1, CLU, and ABCA7, in blood, and (2) examine its applicability to the diagnosis of AD. We examined methylation differences at CpG island shores in the six genes using Sanger sequencing, and one of two groups of 48 AD patients and 48 elderly controls was used for a test or replication analysis. We found that methylation levels in three out of the six genes, CR1, CLU, and PICALM, were significantly lower in AD subjects. The combination of CLU methylation levels and the APOE genotype classified AD patients with AUC = 0.84 and 0.80 in the test and replication analyses, respectively. Our study implicates methylation differences at the CpG island shores of AD-associated genes in the onset of AD and suggests their diagnostic value.

The aim of the present study was to (1) investigate the relationship between late onset AD and DNA methylation levels in the top six Alzheimer's disease (AD)-related genes in blood and (2) examine its applicability to the diagnosis of AD. We examined methylation differences at CpG island shores in the top six genes using Sanger sequencing, and one of two groups of 48 AD patients and 48 elderly controls was used for a test or replication analysis. We found that methylation levels in three out of the six genes, CR1, CLU, and PICALM, were lower in AD subjects. The combination of CLU methylation levels and the APOE genotype classified AD patients with AUC=0.84 and 0.80 in the test and replication analyses, respectively. Our results implicate methylation differences at the CpG island shores of AD-related genes in the onset of AD and suggest their diagnostic value.