Neuronal microRNA response to Alzheimer's disease amyloid beta

In neurodegenerative disorders such as Alzheimer’s disease (AD), brain miRNA profiles are altered; thus miRNA dysfunction could be both a cause and a consequence of disease. Our study dissects the complexity of human AD pathology, in the absence of a post mortem delay, and provides the first miRNA profiling analysis addressing the contribution of amyloid-β (Aβ), a known causative factor of AD, to the de-regulation of neuronal miRNA expression. We used murine primary hippocampal neurons to show that Aβ is a powerful regulator of mature miRNA expression and a prominent miRNA down-regulation is evoked in response to Aβ peptides. Our study provides insight into a previously unexplored mechanism of how Aβ may impact the pathology of AD and identification of key miRNAs affected by Aβ will allow further analysis on target genes and biological pathways contributing to AD pathomechanisms. Mouse primary hippocampal neurons were grown for 23 DIV before being treated for 24 hours with either 5uM amyloid beta (1-42) aged for 24 hours at 37 degrees with shaking, or a PBS control. Total RNA was extracted using the Qiagen miRNeasy Kit and expression of 380 microRNA was analysed using rodent TaqMan low density microRNA microarrays (Applied Biosystems).