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Neurobiol Dis. 2014 Sep;69:124-33. doi: 10.1016/j.nbd.2014.05.018. Epub 2014 May 27.

Interleukin-1β mediated amyloid plaque clearance is independent of CCR2 signaling in the APP/PS1 mouse model of Alzheimer's disease.

Author information

  • 1Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
  • 2Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: kerry_obanion@urmc.rochester.edu.

Abstract

Neuroinflammation is a key component of Alzheimer's disease (AD) pathogenesis. Particularly, the proinflammatory cytokine interleukin-1 beta (IL-1β) is upregulated in human AD and believed to promote amyloid plaque deposition. However, studies from our laboratory have shown that chronic IL-1β overexpression in the APPswe/PSEN1dE9 (APP/PS1) mouse model of AD ameliorates amyloid pathology, increases plaque-associated microglia, and induces recruitment of peripheral immune cells to the brain parenchyma. To investigate the contribution of CCR2 signaling in IL-1β-mediated amyloid plaque clearance, seven month-old APP/PS1/CCR2(-/-) mice were intrahippocampally transduced with a recombinant adeno-associated virus serotype 2 containing the cleaved form of human IL-1β (rAAV2-IL-1β). Four weeks after rAAV2-IL-1β transduction, we found significant reductions in 6E10 and Congo red staining of amyloid plaques that was confirmed by decreased levels of insoluble Aβ1-42 and Aβ1-40 in the inflamed hippocampus. Bone marrow chimeric studies confirmed the presence of infiltrating immune cells following IL-1β overexpression and revealed that dramatic reduction of CCR2(+) peripheral mononuclear cell recruitment to the inflamed hippocampus did not prevent the ability of IL-1β to induce amyloid plaque clearance. These results suggest that infiltrating CCR2(+) monocytes do not contribute to IL-1β-mediated amyloid plaque clearance.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Alzheimer's disease; Bone marrow derived; CCL2; CCR2; Interleukin-1β; Monocytes; Neuroinflammation

PMID:
24874542
[PubMed - indexed for MEDLINE]
PMCID:
PMC4120473
[Available on 2015-09-01]
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