The Role of Small RNAs in Alzheimer's Disease
We aim to describe changes in small RNA species in brain, CSF and plasma to understand the role of small RNAs in Alzheimer's Disease and develop predictive models. In aim 1 we will generate small RNA sequences in brain, CSF and Plasma of individuals with Alzheimer's Disease and Controls. Then, we will use statistical and bioinformatic tools to 1) Describe and understand changes in small RNA proportions and species between cases and controls; and 2) Generate a model that allows disease prediction. In aim 2, we will use neuron-derived induced pluripotent stem cells to investigate the effects of specific small RNAs on the amyloid-beta pathway to understand if small RNAs are part of the causal pathway.
Small RNAs (sRNAs) are short (12-200nt) non-coding regulatory RNAs that balance gene expression. In Alzheimer disease (AD), most of the studies have focused on micro RNAs (miRNAs), but miRNAs are not the most abundant sRNA species in tissues and biofluids. Thus, the relationship between AD pathophysiology and sRNAs beyond miRNAs is mostly unknown and the aim of the present proposal. In this study, one of the aims is to find a set of small RNAs that is specific enough to help in the detection and diagnosis of Alzheimer's Disease (AD). The delivery of a specific and cost-effective diagnostic tool will require further research, but at the completion of this study, we aim to propose a set of small RNAs useful to diagnose Alzheimer's Disease.