Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer’s disease model

• Published in: The Journal of experimental medicine Vol. 217; no. 9
• Main Authors: Wang, Shoutang, Mustafa, Meer, Yuede, Carla M., Salazar, Santiago Viveros, Kong, Philip, Long, Hua, Ward, Michael, Siddiqui, Omer, Paul, Robert, Gilfillan, Susan, Ibrahim, Adiljan, Rhinn, Hervé, Tassi, Ilaria, Rosenthal, Arnon, Schwabe, Tina, Colonna, Marco
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 07.09.2020
• Subjects: Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - pathology; Alzheimer Disease - therapy; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Anxiety - pathology; Biomarkers - cerebrospinal fluid; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - pathology; Cell Proliferation - drug effects; Disease Models, Animal; Humans; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice, Inbred C57BL; Mice, Transgenic; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; Neurites - drug effects; Neurites - pathology; Neuroinflammation; Osteopontin - metabolism; Protein Conformation; Receptors, Immunologic - immunology; Receptors, Immunologic - metabolism; Signal Transduction; Solubility

TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer’s disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, w...