DNA methylation analysis of candidate genes associated with dementia in peripheral blood.

Aim: To investigate whether genes implicated in dementia pathogenesis are differently methylated in peripheral blood. Materials & methods: Participants included 160 cognitively healthy individuals aged 70+ years: 73 who were subsequently diagnosed with dementia and 87 controls matched on age, gender, education, smoking and baseline cognition. A total of 49 participants also provided blood samples at diagnosis. Blood DNA methylation of APOE, APP, BDNF, PIN1, SNCA and TOMM40 was examined. Results: A total of 56 of 299 probes were differentially methylated in dementia compared with controls and 39 probes prior to diagnosis. The greatest effect size was in APP (cg19423170, Δ-8.32%, adjusted p = 0.009 at diagnosis; cg19933173, Δ-4.18%, adjusted p < 0.0001 prediagnosis). Conclusion: Genes implicated in dementia pathogenesis show differential blood methylation in dementia, even prior to diagnosis.