Nasal inoculation of an adenovirus vector encoding 11 tandem repeats of Aβ1-6 upregulates IL-10 expression and reduces amyloid load in a Mo/ Hu APPswe PS1dE9 mouse model of Alzheimer's disease

Academic Article

Abstract

  • Background: One of the pathological hallmarks of Alzheimer's disease (AD) is deposits of amytoid β-peptide (Aβ) in neuritic plaques and cerebral vessels. Immunization of AD mouse models with Aβ reduces Aβ deposits and improves memory and learning deficits. Because recent clinical trials of immunization with Aβ were hatted due to brain inflammation that was presumably induced by a T-cell-mediated autoimmume response, vaccination modalities that elicit predominantly humoral immune responses are currently being developed. Methods: We have nasally immunized a young AD mouse model with an adenovirus vector encoding 11 tandem repeats of Aβ1-6 fused to the receptor-binding domain (Ia) of Pseudomonas evotoocin A (PEDI), AdPEDI-(AβI-6)11, in order to evaluate the efficacy of the vector in preventing Aβ deposits in the brain. We also have investigated immune responses of mice to AdPEDI-(APβ-6)11. Results: Nasal immunization of an AD mouse model with AdPEDI- (Aβl-6)11 elicited a predominant IgG1 response and reduced Aβ load in the brain. The plasma IL-10 level in the AD mouse model was upregulated after immunization and, upon the stimulation with PEDI-(Aβl-6)11, marked IL-10 responses were found in splenic CD4+ T cells from C57BL/6 mice that had been immunized with AdPEDI-(Aβl-6)11. Conclusions: These results suggest that the induction of Th2-biased responses with AdPEDI-(Aβ1-6)11 in mice is mediated in pan through the upregulation of IL-10, which inhibits activation of dendritic cells that dictate the induction of Th1 cells. Copyright © 2007 John Wiley & Sons, Ltd.
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    Author List

  • Kim HD; Tahara K; Maxwell JA; Lalonde R; Fukuiwa T; Fujihashi K; Van Kampen KR; Kong FK; Tang DCC; Fukuchi KI
  • Start Page

  • 88
  • End Page

  • 98
  • Volume

  • 9
  • Issue

  • 2