脑室内人免疫球蛋白在淀粉样蛋白沉积的小鼠模型中广泛分布但无法改善淀粉样蛋白

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

Volume: 11 Issue: 7

Author(s): Aurelie Joly-Amado, Milene Brownlow, Jacob Pierce, Advaitaa Ravipati, Erin Showalter, Qingyou Li, Marcia N Gordon and Dave Morga

Affiliation:

关键词: 行为测试，CD45，刚果红，小胶质细胞活化，旋臂水迷宫，疫苗接种

摘要: 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.

Cite this article as:

Aurelie Joly-Amado, Milene Brownlow, Jacob Pierce, Advaitaa Ravipati, Erin Showalter, Qingyou Li, Marcia N Gordon and Dave Morga , Intraventricular Human Immunoglobulin Distributes Extensively but Fails to Modify Amyloid in a Mouse Model of Amyloid Deposition, Current Alzheimer Research 2014; 11 (7) . https://dx.doi.org/10.2174/1567205011666140812114341