The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances amyloid phagocytosis in a mouse model of Alzheimer's disease

• Published in: Neurobiology of aging Vol. 36; no. 11; pp. 2995 - 3007
• Main Authors: Varnum, Megan M, Kiyota, Tomomi, Ingraham, Kaitlin L, Ikezu, Seiko, Ikezu, Tsuneya
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015
• Subjects: Adeno-associated virus; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Animals; Antigens, CD - pharmacology; Antigens, CD - physiology; CD200; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cells, Cultured; Disease Models, Animal; Hippocampus - cytology; Hippocampus - physiology; Internal Medicine; Mice, Transgenic; Microglia; Microglia - cytology; Microglia - metabolism; Neural Stem Cells - cytology; Neurogenesis - drug effects; Neurogenesis - genetics; Neuroinflammation; Neurology; Phagocytosis - drug effects; Stem Cells - cytology; Transgenic mouse model; Neuroinflammation; Adeno-associated virus; Alzheimer's disease; Transgenic mouse model; CD200; Microglia
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2015.07.027

Abstract Cluster of Differentiation-200 (CD200) is an anti-inflammatory glycoprotein expressed in neurons, T cells, and B cells, and its receptor is expressed on glia. Both Alzheimer's disease patients and mouse models display age-related or amyloid-β peptide (Aβ)-induced reductions in CD200. The goal of this study was to determine if neuronal CD200 expression restores hippocampal neurogenesis and reduces Aβ in the amyloid precursor protein mouse model. Amyloid precursor protein and wild-type mice were injected at 6 months of age with an adeno-associated virus expressing CD200 into the hippocampus and sacrificed at 12 months. CD200 expression restored neural progenitor cell proliferation and differentiation in the subgranular and granular cell layers of the dentate gyrus and reduced diffuse but not thioflavin-S+ plaques in the hippocampus. In vitro studies demonstrated that CD200-stimulated microglia increased neural differentiation of neural stem cells and enhanced axon elongation and dendrite number. CD200 also enhanced Aβ uptake by microglia. These data indicate that CD200 is capable of enhancing microglia-mediated Aβ clearance and neural differentiation and has potential as a therapeutic for Alzheimer's disease.