title: 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).
  
  
  CONCLUSIONS
  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.forename: Isabelle
authors.initials: I
authors.lastname: St-Amour
authors.forename: Isabelle
authors.initials: I
authors.lastname: Paré
authors.forename: Cyntia
authors.initials: C
authors.lastname: Tremblay
authors.forename: Katherine
authors.initials: K
authors.lastname: Coulombe
authors.forename: Renée
authors.initials: R
authors.lastname: Bazin
authors.affiliation: Centre de Recherche du CHU de Québec, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada. Frederic.Calon@pha.ulaval.ca.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000073883:CX3C Chemokine Receptor 1; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D008569:Memory Disorders / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D019707:Receptors, Chemokine / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D019707:Receptors, Chemokine; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins