These authors contributed equally to this study.
Attenuation of AD-like neuropathology by harnessing peripheral immune cells: local elevation of IL-10 and MMP-9
Article first published online: 24 SEP 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 111, Issue 6, pages 1409–1424, December 2009
How to Cite
Koronyo-Hamaoui, M., Ko, M. K., Koronyo, Y., Azoulay, D., Seksenyan, A., Kunis, G., Pham, M., Bakhsheshian, J., Rogeri, P., Black, K. L., Farkas, D. L. and Schwartz, M. (2009), Attenuation of AD-like neuropathology by harnessing peripheral immune cells: local elevation of IL-10 and MMP-9. Journal of Neurochemistry, 111: 1409–1424. doi: 10.1111/j.1471-4159.2009.06402.x
- Issue published online: 20 NOV 2009
- Article first published online: 24 SEP 2009
- Received May 13, 2009; revised manuscript received September 15, 2009; accepted September 15, 2009.
- glial scar;
- matrix metalloproteinases;
Immunization with an altered myelin-derived peptide (MOG45D) improves recovery from acute CNS insults, partially via recruitment of monocyte-derived macrophages that locally display a regulatory activity. Here, we investigated the local alterations in the cellular and molecular immunological milieu associated with attenuation of Alzheimer’s disease-like pathology following immunotherapy. We found that immunization of amyloid precursor protein/presenilin 1 double-transgenic mice with MOG45D peptide, loaded on dendritic cells, led to a substantial reduction of parenchymal and perivascular amyloid beta (Aβ)-plaque burden and soluble Aβ(1–42) peptide levels as well as reduced astrogliosis and levels of a key glial scar protein (chondroitin sulphate proteoglycan). These changes were associated with a shift in the local innate immune response, manifested by increased Iba1+/CD45high macrophages that engulfed Aβ, reduced pro-inflammatory (tumor necrosis factor-α) and increased anti-inflammatory (interleukin-10) cytokines, as well as a significant increase in growth factors (IGF-1 and TGFβ) in the brain. Furthermore, the levels of matrix metalloproteinase-9, an enzyme shown to degrade Aβ and is associated with glial scar formation, were significantly elevated in the brain following immunization. Altogether, these results indicate that boosting systemic immune cells leads to a local immunomodulation manifested by elevated levels of anti-inflammatory cytokines and metalloproteinases that contribute to ameliorating Alzheimer’s disease pathology.