Lower DNA methylation levels in CpG island shores of CR1, CLU, and PICALM genes in the blood of Alzheimer’s disease patients

Abstract

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.