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P3‐338: Beneficial effects of IVIg in the triple transgenic mouse model of Alzheimer's disease
Author(s) -
StAmour Isabelle,
Paré Isabelle,
Tremblay Cyntia,
Calon Frederic,
Bazin Renée
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1562
Subject(s) - medicine , genetically modified mouse , immune system , antibody , immunology , flow cytometry , gastroenterology , transgene , chemistry , biochemistry , gene
Background: Intravenous immunoglobulin preparation (IVIg) is composed of >98% human IgG obtained from the plasma of healthy donors. It is approved for the treatment of immunodeficiency and autoimmune diseases and is under study in Alzheimer disease (AD) as well. Understanding the mechanisms of action of IVIg in AD would allow a more rational use of this product and may lead to the development of replacement therapies. Methods: To this aim, we investigated the effects of IVIg treatment in 3xTg-AD mice, which reproduce both As and tau pathologies. 3xTg-AD mice and non-transgenic controls were injected twice weekly with IVIg (or vehicle) for 1 or 3 months. Results: IVIg did not induce a significant immune response and was detected in the serum (ELISA: 22.2 mg/mL 6 0.7, mean 6 SEM), on splenocytes (flow cytometry: mean fluorescence index: 28.2 6 1.2 versus 7.5 6 0.3. Mean 6 SEM in IVIg and vehicle 3xTg-AD mice, respectively. p<0.0001) and in the parieto-temporal cortex (ELISA: 22.6 6 1.4 ng/mg tissue. Mean 6 SEM) of IVIg-injected mice. Furthermore, following IVIg injections, a significant reduction of behavioral deficits was observed in the object recognition (OR) test (OR index: 0.67 6 0.03 versus 0.55 6 0.03; mean 6 SEM in IVIg and vehicle 3xTg-AD mice, respectively; p1⁄40.0096) but not in the Barnes Maze. IVIg treatment also led to a 22% reduction of the soluble Ab42/Ab40 ratio versus vehicle (p1⁄40.025). Conclusions: Such beneficial effects of IVIg on cognition and Ab42/Ab40 ratio in 3xTgAD mice support the use of this model to further investigate the mechanisms of action of IVIg in AD.