Epigenetic Modulation in Alzheimer's Disease: Function of Hippocampal microRNAs

MicroRNAs (miRNA) are small non-coding RNAs that play a critical role in the regulation of gene expression programs and thus key mediators of cellular homeostasis. There is increasing evidence that deregulation of miRNAs contribute to neurodegenerative diseases and provide in turn novel opportunities to define biomarker signatures and develop novel therapeutic approaches. To develop effective methods for the delivery of therapeutic miRNA to neurons and to define miRNA changes during memory decline is this of utmost importance. In this project I addressed these important questions and could show that the use of modified exosomes might be a suitable approach to deliver miRNA into the brain. In addition I employed next-generation sequencing (NGS) to profile the miRNAome of 4 different brain regions in young and cognitively impaired old mice. I also examined aging- induced changes in blood from the same mice. My observation suggests that aging is associated with a remarkable deregulation of the brain and blood miRNA profile. Target prediction analyses revealed that the age-associated miRNA signature reflects inflammation- associated mechanisms. The data presents to most comprehensive analysis of the age- associated brain miRNAome and forms the basis for further mechanistic studies