Differential DNA methylation profiles of Alzheimer's disease-related genomic pathways in the blood of cognitively-intact individuals with and without high impact chronic pain.

Background: Chronic pain and Alzheimer's disease (AD) are prevalent in older age and their etiologies remain to be understoodand evidence supports potential associations between the two. Both high impact pain and AD have been previously associated with differences in the epigenome. Interactions with the epigenome may serve as a possible underlying mechanism linking high impact pain and AD.

Objective: To complete epigenetic canonical pathways analyses related to AD in individuals with and without high-impact knee pain.

Methods: This manuscript aimed to explore differences in DNA methylation patterns in genes and pathways associated with AD. Blood samples of cognitively intact, community-dwelling adults with high impact knee painmversus pain-free controls were compared on their DNA methylation levels of AD-related genes. Pathway enrichment analysis was performed on significantly different DNA Methylation probes by pain group.

Results: There were significant DNA methylation differences between the high impact versus the pain-free control groups in genes and pathways associated with AD (p < 0.05). We found a total of 17,563 differentially methylated CpG probes, including 13,411 hypermethylated CpG probes and 4152 hypomethylated CpG probes. Further, pathway analysis revealed these differences were significantly associated with AD-related pathways associated with AD progression.

Conclusions: This study sample showed AD-related DNA methylation differences and associated potential canonical pathways in those with and without high impact knee pain. These results highlight the need to study overlapping epigenetic modifications underlying high impact pain and AD pathologies. Further studies, including gene expression, are needed to further explore the relationship between epigenetics, chronic pain, and AD.