TY - JOUR AU - Chen, Wesley AU - Abud, Edsel A. AU - Yeung, Stephen T. AU - Lakatos, Anita AU - Nassi, Trevor AU - Wang, Jane AU - Blum, David AU - Buée, Luc AU - Poon, Wayne W. AU - Blurton-Jones, Mathew PY - 2016 DA - 2016/06/23 TI - Increased tauopathy drives microglia-mediated clearance of beta-amyloid JO - Acta Neuropathologica Communications SP - 63 VL - 4 IS - 1 AB - Alzheimer disease is characterized by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Emerging studies suggest that in neurodegenerative diseases, aggregation of one protein species can promote other proteinopathies and that inflammation plays an important role in this process. To study the interplay between Aβ deposition, tau pathology, and microgliosis, we established a new AD transgenic mouse model by crossing 5xfAD mice with Thy-Tau22 transgenic mice. The resulting ‘T5x’ mice exhibit a greater than three-fold increase in misfolded and hyperphosphorylated tau and further substantiates the hypothesis that Aβ accelerates tau pathology. Surprisingly, T5x mice exhibit a 40-50 % reduction in Aβ plaque load and insoluble Aβ species when compared with aged-matched 5xfAD littermates. T5x mice exhibit significant changes in cytokine production, an almost doubling of microglial number, and a dramatic shift in microglia activation state. Furthermore, T5x microglia exhibit increased phagocytic capacity that enhances the clearance of insoluble Aβ and decreasing plaque load. Therefore, our results suggest that strategies to increase the phagocytic ability of microglia can be employed to reduce Aβ and that tau-induced changes in microglial activation state can promote the clearance of Aβ. SN - 2051-5960 UR - https://doi.org/10.1186/s40478-016-0336-1 DO - 10.1186/s40478-016-0336-1 ID - Chen2016 ER -