TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease

• Published in: Neuron (Cambridge, Mass.) Vol. 103; no. 5; pp. 820 - 835.e7
• Main Authors: Griciuc, Ana, Patel, Shaun, Federico, Anthony N., Choi, Se Hoon, Innes, Brendan J., Oram, Mary K., Cereghetti, Gea, McGinty, Danielle, Anselmo, Anthony, Sadreyev, Ruslan I., Hickman, Suzanne E., El Khoury, Joseph, Colonna, Marco, Tanzi, Rudolph E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.09.2019; Elsevier Limited
• Subjects: Acute-Phase Reaction - genetics; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's; Alzheimer's disease; amyloid beta; Amyloid beta-Peptides - metabolism; Animals; Brain - metabolism; Brain - pathology; CD33; Cell adhesion & migration; Chemokines; Cognition; Cognitive ability; Cytokines; Datasets; Disease Models, Animal; Gene expression; Gene Expression Regulation; IL-1beta; IL-1β; Interleukin 1 receptors; Interleukin 6; Interleukin 8; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Membrane Glycoproteins - genetics; Memory; Mice; Mice, Knockout; Microglia; Microglia - metabolism; Microglia - pathology; Neurodegeneration; neuroinflammation; Pathology; pathway analysis; Phagocytosis; Phagocytosis - genetics; Plaque, Amyloid - pathology; Receptors, Immunologic - genetics; Retention; Ribonucleic acid; RNA; RNA-seq; Sialic Acid Binding Ig-like Lectin 3 - genetics; Software; Statistical analysis; transcriptomics; TREM2; RNA-seq; neuroinflammation; transcriptomics; TREM2; pathway analysis; microglia; IL-1beta; CD33; amyloid beta; Alzheimer's
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2019.06.010

The microglial receptors CD33 and TREM2 have been associated with risk for Alzheimer’s disease (AD). Here, we investigated crosstalk between CD33 and TREM2. We showed that knockout of CD33 attenuated amyloid beta (Aβ) pathology and improved cognition in 5xFAD mice, both of which were abrogated by ad...