title: Nasal inoculation of an adenovirus vector encoding 11 tandem repeats of Abeta1-6 upregulates IL-10 expression and reduces amyloid load in a Mo/Hu APPswe PS1dE9 mouse model of Alzheimer's disease.
abstract: BACKGROUND
  One of the pathological hallmarks of Alzheimer's disease (AD) is deposits of amyloid beta-peptide (Abeta) in neuritic plaques and cerebral vessels. Immunization of AD mouse models with Abeta reduces Abeta deposits and improves memory and learning deficits. Because recent clinical trials of immunization with Abeta were halted due to brain inflammation that was presumably induced by a T-cell-mediated autoimmune 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 Abeta1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A (PEDI), AdPEDI-(Abeta1-6)(11), in order to evaluate the efficacy of the vector in preventing Abeta deposits in the brain. We also have investigated immune responses of mice to AdPEDI-(Abeta1-6)(11).
  
  
  RESULTS
  Nasal immunization of an AD mouse model with AdPEDI-(Abeta1-6)(11) elicited a predominant IgG1 response and reduced Abeta load in the brain. The plasma IL-10 level in the AD mouse model was upregulated after immunization and, upon the stimulation with PEDI-(Abeta1-6)(11), marked IL-10 responses were found in splenic CD4(+) T cells from C57BL/6 mice that had been immunized with AdPEDI-(Abeta1-6)(11).
  
  
  CONCLUSIONS
  These results suggest that the induction of Th2-biased responses with AdPEDI-(Abeta1-6)(11) in mice is mediated in part through the upregulation of IL-10, which inhibits activation of dendritic cells that dictate the induction of Th1 cells.
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, PO Box 1649, Peoria, IL 61656, USA.
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Kim
authors.forename: Kazuki
authors.initials: K
authors.lastname: Tahara
authors.forename: J Adam
authors.initials: JA
authors.lastname: Maxwell
authors.forename: Robert
authors.initials: R
authors.lastname: Lalonde
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fukuiwa
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Kent R
authors.initials: KR
authors.lastname: Van Kampen
authors.forename: Fan-Kun
authors.initials: FK
authors.lastname: Kong
authors.forename: De-chu C
authors.initials: DC
authors.lastname: Tang
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Fukuchi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D023582:Alzheimer Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000008:administration & dosage*; D007074:Immunoglobulin G / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology; D020080:Tandem Repeat Sequences; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
chemical_list: D023582:Alzheimer Vaccines; D000682:Amyloid; D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D010446:Peptide Fragments; D019444:Vaccines, DNA; C505239:amyloid beta-protein (1-6); D016753:Interleukin-10