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

Megan M. Varnum, Tomomi Kiyota, Kaitlin L. Ingraham, Seiko Ikezu, Tsuneya Ikezu

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2995-3007
Number of pages13
JournalNeurobiology of Aging
Volume36
Issue number11
DOIs
StatePublished - Nov 2015

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Neurogenesis
Microglia
Phagocytosis
Amyloid
Glycoproteins
Alzheimer Disease
Anti-Inflammatory Agents
Amyloid beta-Protein Precursor
Hippocampus
Serum Amyloid A Protein
Dependovirus
Neural Stem Cells
Dentate Gyrus
Dendrites
Neuroglia
Axons
Cell Differentiation
B-Lymphocytes
Stem Cells
Cell Proliferation

Keywords

  • Adeno-associated virus
  • Alzheimer's disease
  • CD200
  • Microglia
  • Neuroinflammation
  • Transgenic mouse model

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances amyloid phagocytosis in a mouse model of Alzheimer's disease. / Varnum, Megan M.; Kiyota, Tomomi; Ingraham, Kaitlin L.; Ikezu, Seiko; Ikezu, Tsuneya.

In: Neurobiology of Aging, Vol. 36, No. 11, 11.2015, p. 2995-3007.

Research output: Contribution to journalArticle

Varnum, Megan M. ; Kiyota, Tomomi ; Ingraham, Kaitlin L. ; Ikezu, Seiko ; Ikezu, Tsuneya. / The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances amyloid phagocytosis in a mouse model of Alzheimer's disease. In: Neurobiology of Aging. 2015 ; Vol. 36, No. 11. pp. 2995-3007.
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