JAEPRE23 - 39 Studying the cell-type role of KMT5s in Alzheimer's disease: new therapeutical targets

Our laboratory is interested in understanding the aberrant molecular changes underlying cognitive deficits in physiological and pathological brain ageing, with particular interest in Alzheimer’s disease. We hypothesise that the interaction between the environment and genetics favours long-lasting cell-type molecular changes in the brain, which will impact cognitive function with time. Thus, our laboratory is interested in studying the contribution of cell-type neuro-epigenetics to cognitive function in the ageing brain. Among the different epigenetic regulations, we are interested in studying how histone post-translational modifications regulate gene transcription during memory formation and how these fundamental mechanisms are aberrantly regulated during physiological and pathological brain ageing. We have shown that memory-induced stimulation favours the chromatin remodelling of genes involved in memory formation and that such processes are aberrantly regulated in the ageing brain or in response to amyloid beta, the toxic peptide associated with Alzheimer’s disease. Given the role of different cell-types in memory formation or their involvement in neurodegeneration, we are now dissecting the cell-type neuro-epigenetics of brain cells (neurons, astrocytes, microglia and oligodendrocytes) in relation to physiological and pathological brain processes. To achieve our research goals, we use a range of experimental settings from cell cultures and mouse models to hum