Microglial complement receptor 3 regulates brain Aβ levels through secreted proteolytic activity

• DOI: 10.1084/jem.20162011
• Publication Date: 2017-03-15T14:10:09Z
• Authors: Eva Czirr; Nicholas A. Castello; Kira I. Mosher; Joseph M. Castellano; Izumi V. Hinkson; Kurt M. Lucin; Bernat Baeza-Raja; Jae Kyu Ryu; Lulin Li; Sasha N. Farina; Nadia P. Belichenko; Frank M. Longo; Katerina Akassoglou; Markus Britschgi; John R. Cirrito; Tony Wyss-Coray
• Keywords: Microdialysis; TREM2; Amyloid (mycology)

Recent genetic evidence supports a link between microglia and the complement system in Alzheimer’s disease (AD). In this study, we uncovered novel role for microglial receptor 3 (CR3) regulation of soluble β-amyloid (Aβ) clearance independent phagocytosis. Unexpectedly, ablation CR3 human amyloid precursor protein–transgenic mice results decreased, rather than increased, Aβ accumulation. line with these findings, cultured lacking are more efficient wild-type cells at degrading extracellular by secreting enzymatic factors, including tissue plasminogen activator. Furthermore, small molecule modulator reduces levels half-life brain interstitial fluid (ISF), as measured vivo microdialysis. These suggest that limits from ISF, illustrating metabolism defining potential new therapeutic target AD.