Abstract:

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.

日本語要旨:

血液中のDNAメチル化レベルの違いがアルツハイマー型認知症の診断的価値があること示した。AD患者と健常人の末梢血由来のDNAから6つのAD関連遺伝子のCpGアイランドショアでのメチル化レベルを調べたところCR1,CLU,およびPICALMのメチル化レベルがAD群で低くなっており、CLUのメチル化レベルとAPOE遺伝子型を組み合わることで、AD患者に分類できることを示した（学習群：AUC=0.84、再現群：AUC=0.80）。