Artificial Intelligence and Circulating Cell-Free DNA Methylation Profiling: Mechanism and Detection of Alzheimer's Disease.
BACKGROUND: Despite extensive efforts, significant gaps remain in our understanding of Alzheimer's disease (AD) pathophysiology. Novel approaches using circulating cell-free DNA (cfDNA) have the potential to revolutionize our understanding of neurodegenerative disorders.
METHODS: We performed DNA methylation profiling of cfDNA from AD patients and compared them to cognitively normal controls. Six Artificial Intelligence (AI) platforms were utilized for the diagnosis of AD while enrichment analysis was used to elucidate the pathogenesis of AD.
RESULTS: A total of 3684 CpGs were significantly (adj.
CONCLUSION: We describe numerous epigenetically altered genes which were previously reported to be differentially expressed in the brain of AD sufferers. Genes identified by AI to be the best predictors of AD were either known to be expressed in the brain or have been previously linked to AD. We highlight enrichment in the Calcium signaling pathway, Glutamatergic synapse, Hedgehog signaling pathway, Axon guidance and Olfactory transduction in AD sufferers. To the best of our knowledge, this is the first reported genome-wide DNA methylation study using cfDNA to detect AD.
Bahado-Singh RO, Radhakrishna U, Gordevičius J, Aydas B, Yilmaz A, Jafar F, et al. [Imam K, Challapalli K, Graham SF] Artificial intelligence and circulating cell-free DNA methylation profiling: mechanism and detection of Alzheimer's disease. Cells. 2022 May 25;11(11):1744. doi: 10.3390/cells11111744. PMID: 35681440.