Grant: Project Grant

Inflammation of the brain is a hallmark of many neurodegenerative disorders including age -related dementias caused by a protein called TDP-43. Immune cells of the brain responsible for this inflammatory state are called microglia. Evidence suggests that chronic activation of these cells contributes to neurodenegerative processes in the brain, therefore these cells may be considered as a potential target for therapeutic modulation. Our preliminary results revealed that in the context of dementias caused by protein TDP-43, microglial cells express a very high level of protein tau. We also found that further increasing the level of tau exacerbates TDP-43 mediated pathology and precipitates a clinical onset of cognitive deficits. Based on our exciting preliminary results, we propose that chronic inflammation markedly increases the level of tau in microglial cells which in turn may contribute to disease progression. At present, the role tau in microglial cells as well as in TDP-43 mediated dementias is not well understood. Therefore, in this proposal we will first examine how increased levels of tau affects function of these cells and, as a next step, we will investigate whether targeting microglial tau has a therapeutic potential in TDP-43 mediated brain disorders.