title: Intraventricular human immunoglobulin distributes extensively but fails to modify amyloid in a mouse model of amyloid deposition.
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 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.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Joly-Amado
authors.forename: Milene
authors.initials: M
authors.lastname: Brownlow
authors.forename: Jacob
authors.initials: J
authors.lastname: Pierce
authors.forename: Advaitaa
authors.initials: A
authors.lastname: Ravipati
authors.forename: Erin
authors.initials: E
authors.lastname: Showalter
authors.forename: Qingyou
authors.initials: Q
authors.lastname: Li
authors.forename: Marcia N
authors.initials: MN
authors.lastname: Gordon
authors.affiliation: USF Health Byrd Alzheimer's Institute, 4001 E. Fletcher Ave. Tampa FL 33613, USA. scientist.dave@gmail.com.
authors.forename: Dave
authors.initials: D
authors.lastname: Morgan
mesh_terms: D000375:Aging; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000686:Amyloidosis / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000008:administration & dosage*; D057967:Infusions, Intraventricular; D018782:Maze Learning; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D058225:Plaque, Amyloid / Q000473:pathology
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D007074:Immunoglobulin G; D007155:Immunologic Factors