Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model

Chronic activation of brain innate immunity is a prominent feature of Alzheimer’s disease (AD) and primary tauopathies. However, to what degree innate immunity contributes to neurodegeneration as compared with pathological protein-induced neurotoxicity, and the requirement of a particular glial cell type in neurodegeneration, are still unclear. Here we demonstrate that microglia-mediated damage, rather than pathological tau-induced direct neurotoxicity, is the leading force driving neurodegeneration in a tauopathy mouse model. Importantly, the progression of ptau pathology is also driven by microglia. In addition, we found that APOE, the strongest genetic risk factor for AD, regulates neurodegeneration…

• FF
  Foundation for Barnes-Jewish Hospital
• JF
  JPB Foundation
• CA
  Cure Alzheimer's Fund
• CD
  Children's Discovery Institute

  Award: CDI-CORE-2015-505
• IP
  Idorsia Pharmaceuticals
• P
  Plexxikon
• NI
  National Institutes of Health

  Awards: AG047644, NS090934
• G
  Genentech
• WU
  Washington University School of Medicine in St. Louis
• CF
  Center for Cellular Imaging, Washington University