Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model

• DOI: 10.1084/jem.20190980
• Publication Date: 2019-10-10T19:05:48Z
• Authors: Yang Shi; Melissa Manis; Justin Long; Kairuo Wang; Patrick M. Sullivan; Javier Remolina S...; Rosa Hoyle; David M. Holtzman
• Keywords: Tauopathy; Neurotoxicity

Chronic activation of brain innate immunity is a prominent feature Alzheimer's disease (AD) and primary tauopathies. However, to what degree contributes neurodegeneration as compared with pathological protein-induced neurotoxicity, the requirement particular glial cell type in neurodegeneration, are still unclear. Here we demonstrate that microglia-mediated damage, rather than tau-induced direct leading force driving tauopathy mouse model. Importantly, progression ptau pathology also driven by microglia. In addition, found APOE, strongest genetic risk factor for AD, regulates predominantly modulating microglial activation, although minor role apoE regulating insoluble tau formation independent its immunomodulatory function was identified. Our results suggest therapeutic strategies targeting microglia may represent an effective approach prevent setting tauopathy.