Reduced levels of N6-methyladenosine in RNA of peripheral blood mononuclear cells from patients with Alzheimer's disease

Abstract Background Alzheimer's disease (AD) is the leading cause of dementia, yet its underlying causes remain unknown. Increasing evidence supports a role for epigenetic modifications in AD pathogenesis. N6-methyladenosine (m6A), the most common RNA modification, is critical for learning and memory, and its abnormal presence has been observed in the brains of AD patients and animal models. Methods To compare levels of m6A in RNA as well as expression of the responsible enzymes in peripheral blood mononuclear cells (PBMCs) between AD patients and healthy controls. 42 AD patients and 42 age-matched healthy controls were prospectively enrolled from the Affiliated Hospital of Jining Medical University. m6A levels in RNA were quantified and expressions of m6A-related proteins and mRNA were examined. Genome-wide profiling of m6A-tagged transcripts was performed by m6A-modified RNA immunoprecipitation sequencing and RNA sequencing. Results Lower levels of m6A in PBMCs RNA in AD patients compared to controls, as well as downregulation of m6A methyltransferase and demethylase components. Dysregulation of m6A was associated with upregulation of m6A at 230 loci and downregulation at 163 loci, resulting in altered expression of disease-related genes. Conclusion Dysregulation of m6A in RNA may play a role in AD pathogenesis and may provide new avenues for diagnosis and treatment.