A microRNA signature for early detection and RNA therapy in Alzheimer´s disease (miR-181a-5p)
Since changes in cognitive function develop slowly over time, Alzheimer's disease patients are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for inexpensive and minimal invasive biomarker that could be used in screening approaches with the aim to identify individuals at risk, that can then undergo further diagnostics and eventually stratified therapies. In this study we use an integrative approach combining the analysis of human data and model systems to identify a circulating 3-microRNA signature that reflect key processes linked to neural homeostasis and informs about cognitive decline. We furthermore provide evidence that expression changes of this signature represent relevant patho-mechanisms in the brain and are a suitable target for RNA therapeutics towards dementia. Overall design: Analysis of RNAseq data from primary hippocampal neurons treated with lipid nanoparticles packaged with either miR-181a-5p mimic or negative control siRNA