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
✍ Scribed by Hong-Duck Kim; Kazuki Tahara; J. Adam Maxwell; Robert Lalonde; Tatsuya Fukuiwa; Kohtaro Fujihashi; Kent R. Van Kampen; Fan-Kun Kong; De-chu C. Tang; Ken-ichiro Fukuchi
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 394 KB
- Volume
- 9
- Category
- Article
- ISSN
- 1099-498X
- DOI
- 10.1002/jgm.993
No coin nor oath required. For personal study only.
✦ Synopsis
Background One of the pathological hallmarks of Alzheimer's disease (AD) is deposits of amyloid 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 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 Aβ1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A (PEDI), AdPEDI-(Aβ1-6) 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-(Aβ1-6) 11 .
Results Nasal immunization of an AD mouse model with AdPEDI-(Aβ1-6) 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-(Aβ1-6) 11 , marked IL-10 responses were found in splenic CD4 + T cells from C57BL/6 mice that had been immunized with AdPEDI-(Aβ1-6) 11 .
Conclusions These results suggest that the induction of Th2-biased responses with AdPEDI-(Aβ1-6) 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.