Intraventricular Human Immunoglobulin Distributes Extensively but Fails to Modify Amyloid in a Mouse Model of Amyloid Deposition
Marcia N Gordon,
Intravenous immunoglobulin infusions into Alzheimer patients have been found to provide cognitive benefit
over a period of 6 mo in open label studies. One suggestion has been that these preparations contain small amounts of antibodies
directed against monomeric and oligomeric Aβ which underlie their effectiveness in patients. To test this hypothesis,
we infused Gammagard®, a version of intravenous immunoglobulin (IVIG), into the lateral ventricle of amyloid
precursor protein (APP) transgenic mice with pre-existing amyloid deposits. Mice were infused over 4 weeks, and tested
behaviorally for the last 2 weeks of treatment. Brains were analyzed for histopathology. We found widespread distribution
of human–immunoglobulin G (h-IgG) staining in the mouse forebrain, including cerebral cortices and hippocampus. Some
cortical neurons appeared to concentrate the h-IgG, but we did not detect evidence of amyloid plaque labeling by h-IgG.
The IVIG-treated mice had no change in phenotype compared to saline-infused animals with respect to activity, learning
and memory, or amyloid deposition. APP mice infused with an anti-Aβ monoclonal antibody did show some reduction in
amyloid deposits. These data do not support the argument that anti-Aβ antibodies in IVIG preparations are responsible for
cognitive benefits seen with these preparations.
Keywords: Behavioral testing, CD45, congo red, microglial activation, radial arm water maze, vaccination.
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