Abstract

Gammagard IVIg is a therapeutic approach to treat Alzheimer's disease currently in phase 3 clinical trials. Despite the reported efficacy of the approach the mechanism of action is poorly understood. We have previously shown that intracranial injection of anti-Aβ antibodies into the frontal cortex and hippocampus reveals important information regarding the time course of events once the agent is in the brain. In the current study we compared IVIg, mouse-pooled IgG, and the anti-Aβ antibody 6E10 injected intracranially into the frontal cortex and hippocampus of 7-month-old APP/PS1 mice. We established a time course of events ranging from 1 to 21 d postinjection.

IVIg and pooled mouse IgG both significantly reduced Aβ deposition to the same degree as the 6E10 anti-Aβ antibody; however, the clearance was much slower to occur, happening between the 3 and 7 d time points. In contrast, as we have previously shown, Aβ reductions were apparent with the 6E10 anti-Aβ group at the 1 d time point. Also, neuroinflammatory profiles were significantly altered by the antibody treatments. APP/PS1 transgenic mice at 7 months of age typically exhibit an M2a inflammatory phenotype. All antibody treatments stimulated an M2b response, yet anti-Aβ antibody was a more rapid change. Because the neuroinflammatory switch occurs before the detectable reductions in amyloid deposition, we hypothesize that the IVIg and pooled mouse IgG act as immune modulators and this immune modulation is responsible for the reductions in amyloid pathology.

Document Type

Article

Publication Date

6-5-2013

Notes/Citation Information

Published in The Journal of Neuroscience, v. 33, issue 23, p. 9684-9692.

Copyright © 2013 the authors

This article is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (https://creativecommons.org/licenses/by-nc-sa/3.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1523/JNEUROSCI.1220-13.2013

Funding Information

This work was funded by a Baxter Biosciences research grant, and National Institutes of Health Grants NS079637 (D.M.W.) and P20GM103486 (D.M.W.).

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