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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

• Authors: Isabelle St-Amour, Isabelle Paré, Cyntia Tremblay, Katherine Coulombe, Renée Bazin, Frédéric Calon
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 11 Pg. 54 (Mar 22 2014) ISSN: 1742-2094 [Electronic] England
• PMID: 24655894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• CX3C Chemokine Receptor 1
• Cx3cr1 protein, mouse
• Cytokines
• Immunoglobulins, Intravenous
• Immunologic Factors
• PSEN1 protein, human
• Peptide Fragments
• Presenilin-1
• Receptors, Chemokine
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• tau Proteins

Topics

• Alzheimer Disease (complications, drug therapy, genetics, pathology)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Anxiety (drug therapy, etiology)
• Brain (drug effects, metabolism, pathology)
• CX3C Chemokine Receptor 1
• Cytokines (metabolism)
• Disease Models, Animal
• Flow Cytometry
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Immunologic Factors (therapeutic use)
• Memory Disorders (etiology, genetics, prevention & control)
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation (genetics)
• Peptide Fragments (metabolism)
• Presenilin-1 (genetics)
• Receptors, Chemokine (metabolism)
• tau Proteins (genetics)