Progressive memory loss is one of t

Progressive memory loss is one of the most common characteristics of Alzheimer'sdisease (AD), which has been shown to be caused by several factors including ac-cumulation of amyloid β peptide (Aβ) plaques and neurofibrillary tangles. Synapticplasticity and associative plasticity, the cellular basis of memory, are impaired in AD.Recent studies suggest a functional relevance of microRNAs (miRNAs) in regulatingplasticity changes in AD, as their differential expressions were reported in many ADbrain regions. However, the specific role of these miRNAs in AD has not been elu-cidated. We have reported earlier that late long-term potentiation (late LTP) and itsassociative mechanisms such as synaptic tagging and capture (STC) were impairedin Aβ (1–42)-induced AD condition. This study demonstrates that expression of miR-134-5p, a brain-specific miRNA is upregulated in Aβ (1–42)-treated AD hippocampus.Interestingly, the loss of function of miR-134-5p restored late LTP and STC in AD.In AD brains, inhibition of miR-134-5p elevated the expression of plasticity-relatedproteins (PRPs), cAMP-response-element binding protein (CREB-1) and brain-derivedneurotrophic factor (BDNF), which are otherwise downregulated in AD condition.The results provide the first evidence that the miR-134-mediated post-transcrip-tional regulation of CREB-1 and BDNF is an important molecular mechanism under-lying the plasticity deficit in AD; thus demonstrating the critical role of miR-134-5p asa potential therapeutic target for restoring plasticity in AD condition.