Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism

• Published in: The Journal of experimental medicine Vol. 215; no. 3; pp. 745 - 760
• Main Authors: Song, Wilbur M., Joshita, Satoru, Zhou, Yingyue, Ulland, Tyler K., Gilfillan, Susan, Colonna, Marco
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 05.03.2018; The Rockefeller University Press
• Subjects: Activation; ADAM17 Protein - metabolism; Alzheimer's disease; Amyloid; Animal models; Animals; Brain - pathology; Cell Count; Dementia disorders; Gene polymorphism; Genome-wide association studies; Genomes; Gliosis - genetics; Gliosis - pathology; Health risks; Humans; Lipids; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Transgenic; Microglia; Microglia - metabolism; Myeloid Cells - metabolism; Myeloid Cells - pathology; Neurons; Neurons - metabolism; Polymorphism; Polymorphism, Single Nucleotide - genetics; Proteolysis; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Senile plaques; Solubility; Transgenic mice

Alzheimer’s disease (AD) is a neurodegenerative disease that causes late-onset dementia. The R47H variant of the microglial receptor TREM2 triples AD risk in genome-wide association studies. In mouse AD models, TREM2-deficient microglia fail to proliferate and cluster around the amyloid-β plaques ch...