The interplay between micro RNAs and genetic liability to Alzheimer's Disease on memory trajectories in the general population

Abstract

Deficits in cognitive function and memory are common early symptoms of neurodegenerative disorders, such as Alzheimer's Disease (AD). Several studies have discussed micro RNAs (miRNAs) as potential epigenetic early detection biomarkers. In a longitudinal general population sample (n = 548) from the Study of Health in Pomerania, we analyzed the associations between 167 baseline miRNA levels and changes in verbal memory scores with a mean follow-up time of 7.4 years. We additionally assessed the impact of an individual's genetic liability for AD on verbal memory scores in n = 2,334 subjects and a possible interactions between epigenetic and genetic markers. Results revealed two miRNAs associated with changes in immediate verbal memory over time. In interaction analyses between miRNAs and a polygenic risk score for AD, five miRNAs showed a significant interaction effect on changes in verbal memory. All of these miRNAs have previously been identified in the context of AD, neurodegeneration or cognition. Our study provides candidate miRNAs for a decline in verbal memory as an early symptom of neurodegeneration and AD. Further experimental studies are needed to verify the diagnostic value of these miRNA markers in the prodromal stage of AD.

Keywords: Alzheimer polygenic score; Biomarkers; Interaction analyses; hsa-miR-19a-3p; hsa-miR-485-3p; micro RNAs.