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Intraventricular Human Immunoglobulin Distributes Extensively but Fails to Modify Amyloid in a Mouse Model of Amyloid Deposition

[ Vol. 11 , Issue. 7 ]

Author(s):

Aurelie Joly-Amado, Milene Brownlow, Jacob Pierce, Advaitaa Ravipati, Erin Showalter, Qingyou Li, Marcia N Gordon and Dave Morgan   Pages 664 - 671 ( 8 )

Abstract:


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 A β 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-A β monoclonal antibody did show some reduction in amyloid deposits. These data do not support the argument that anti-A β 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.

Affiliation:

USF Health Byrd Alzheimer's Institute, 4001 E. Fletcher Ave. Tampa FL 33613, USA.



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