Many roles of microRNA in Alzheimer's
AD is a neurodegenerative disorder, characterised by synapse loss, extracellular amyloid plaque composed of amyloid-β peptide (Aβ) and intracellular aggregates of hyper-phosphorylated Tau protein. Understanding the molecular mechanisms leading to AD will offer the possibility to identify novel therapeutic targets for its treatment. Increasing evidence points at the importance of expression deregulation of microRNAs (miRNAs) in the development of neurodegenerative diseases. The EU-funded project EMIRAD was dedicated to examining the role of miRNAs in AD. Scientists investigated whether deregulation of miRNAs expression can be used to diagnose AD. They profiled miRNAs isolated from samples of cerebrospinal fluid (CSF) of AD patients and age-matched healthy control subjects. They found that the levels of one of the miRNAs (miR-27a-3p) were significantly reduced in the CSF of AD patients. Researchers also confirmed that mRNAs encoding for AD-relevant proteins are indeed targets of this miRNA. Interestingly, the expression levels of miRNA in CSF drawn before and after death were not correlated. That means that CSF from living patients should be studied for biomarker discovery. Next, the team addressed deregulation of miRNAs in the AD brain. Nanostring molecular counting, deep-sequencing and quantitative PCR allowed profiling of miRNAs in the prefrontal cortex and hippocampus of AD patients and healthy control subjects. A different miRNA (miR-132-3p) was consistently down-regulated in the AD brain. In situ hybridisation and immunostaining methods showed that neurons with lower expression of miR-132-3p also had higher levels of phosphorylated Tau, an AD-relevant protein. EMIRAD increased understanding of the roles of miRNAs in AD pathology. Measuring the expression levels of miR-27a-3p in CSF can be helpful for AD diagnosis and monitoring. Down regulation of miR-132-3p in AD contributes to AD pathology. The results are described in two peer-reviewed scientific publications, Neurology and EMBO Molecular Medicine.
