IVIg protects the 3xTg-AD mouse model of Alzheimer's disease from memory deficit and Aβ pathology.

Publication Type:

Journal Article


J Neuroinflammation, Volume 11, p.54 (2014)


Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Anxiety, Brain, CX3C Chemokine Receptor 1, Cytokines, Disease Models, Animal, Flow Cytometry, Humans, Immunoglobulins, Intravenous, Immunologic Factors, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Peptide Fragments, Presenilin-1, Receptors, Chemokine, tau Proteins


<p><b>BACKGROUND: </b>Intravenous immunoglobulin (IVIg) is currently in clinical study for Alzheimer's disease (AD). However, preclinical investigations are required to better understand AD-relevant outcomes of IVIg treatment and develop replacement therapies in case of unsustainable supply.</p><p><b>METHODS: </b>We investigated the effects of IVIg in the 3xTg-AD mouse model, which reproduces both Aβ and tau pathologies. Mice were injected twice weekly with 1.5 g/kg IVIg for 1 or 3 months.</p><p><b>RESULTS: </b>IVIg induced a modest but significant improvement in memory in the novel object recognition test and attenuated anxiety-like behavior in 3xTg-AD mice. We observed a correction of immunologic defects present in 3xTg-AD mice (-22% CD4/CD8 blood ratio; -17% IL-5/IL-10 ratio in the cortex) and a modulation of CX3CR1+ cell population (-13% in the bone marrow). IVIg treatment led to limited effects on tau pathology but resulted in a 22% reduction of the soluble Aβ42/Aβ40 ratio and a 60% decrease in concentrations of 56 kDa Aβ oligomers (Aβ*56).</p><p><b>CONCLUSION: </b>The memory-enhancing effect of IVIg reported here suggests that Aβ oligomers, effector T cells and the fractalkine pathway are potential pharmacological targets of IVIg in AD.</p>

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