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Abnormal methylation of numerous genes responsible for regulation of transcription, DNA replication, and apoptosis has been linked to Alzheimer\u2019s disease (AD) pathology. We have recently performed whole transcriptome profiling of familial early\u2010onset Alzheimer\u2019s disease (fEOAD) patient\u2010derived fibroblasts. On this basis, we demonstrated a strong dysregulation of cell cycle checkpoints and DNA damage response (DDR) in both fibroblasts and reprogrammed neurons. Here, we show that the aging\u2010correlated hypermethylation of <jats:italic>KLF14<\/jats:italic> and <jats:italic>TRIM59<\/jats:italic> genes associates with abnormalities in DNA repair and cell cycle control in fEOAD. Based on the resulting transcriptome networks, we found that the hypermethylation of <jats:italic>KLF14<\/jats:italic> might be associated with epigenetic regulation of the chromatin organization and mRNA processing followed by hypermethylation of <jats:italic>TRIM59<\/jats:italic> likely associated with the G2\/M cell cycle phase and p53 role in DNA repair with BRCA1 protein as the key player. We propose that the hypermethylation of <jats:italic>KLF14<\/jats:italic> could constitute a superior epigenetic mechanism for <jats:italic>TRIM59<\/jats:italic> hypermethylation. The methylation status of both genes affects genome stability and might contribute to proapoptotic signaling in AD. Since this study combines data obtained from various tissues from AD patients, it reinforces the view that the genetic methylation status in the blood may be a valuable predictor of molecular processes occurring in affected tissues. Further research is necessary to define a detailed role of TRIM59 and KLF4 in neurodegeneration of neurons.<\/jats:p>","DOI":"10.1155\/2018\/6918797","type":"journal-article","created":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T23:31:22Z","timestamp":1522884682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Hypermethylation of <i>TRIM59<\/i> and <i>KLF14<\/i> Influences Cell Death Signaling in Familial Alzheimer\u2019s 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