DNA methylation in peripheral blood leukocytes in late onset Alzheimer's disease.

BACKGROUND

Chronic systemic inflammation is implicated in Alzheimer's disease (AD) pathogenesis and has measurable effects on blood cells. There is increasing interest in non-invasive diagnostic tools that use blood-based biomarkers for AD, such as DNA methylation. Notably, DNA methylation changes in blood are also linked to systemic inflammation. The evaluation of DNA methylation profiles in peripheral blood leukocytes as potential biomarkers for AD is promising.

OBJECTIVE

To determine DNA methylation patterns in blood for AD, and to explore specific blood CpG sites that act as surrogates for brain-tissue methylation.

METHODS

DNA methylation data from peripheral blood leukocytes of AD patients and controls were obtained from the Gene Expression Omnibus (GSE59685 and GSE53740). Differential methylation analysis was performed for individual CpGs Differentially methylated positions (DMPs) and regions with multiple probes (DMRs) and the intersection analysis of DMPs and DMRs was conducted. Functional enrichment analysis highlights relevant biological processes. Furthermore, previously validated specific CpGs used as surrogate of brain tissue were explored.

RESULTS

DNA methylation patterns included , , , and top genes ordered by statistical significance were found in the intersection of DMP and DMR. Differential methylation analyses revealed differentially methylated genes including , , , , , , and . Gene enrichment analysis showed immune processes and intracellular signaling disruptions. Surrogate genes from brain found differentially methylated were and .

CONCLUSIONS

This study identified DNA methylation patterns in peripheral blood leukocytes as potential biomarkers for AD. These findings offer insights into epigenetic mechanisms associated with systemic peripheral inflammation in AD.