Reduced effectiveness of Aβ1-42 immunization in APP transgenic mice with significant amyloid deposition

Vaccinations with Aβ1-42 have been shown to reduce amyloid burden in transgenic models of Alzheimer's disease (AD). We have further tested the efficacy of Aβ1-42 immunization in the Tg2576 mouse model of AD by immunizing one group of mice with minimal Aβ deposition, one group of mice with modest Aβ deposition, and one group with significant Aβ deposition. The effects of immunization on Aβ deposition were examined using biochemical and immunohistochemical methods. In Tg2576 mice immunized prior to significant amyloid deposition, Aβ1-42 immunization was highly effective. Biochemically extracted Aβ40 and Aβ42 levels were significantly reduced and immunohistochemical plaque load was also reduced. Immunization of mice with modest amounts of pre-existing Aβ deposits selectively reduced Aβ42 without altering Aβ40, although plaque load was reduced. In contrast, in Tg2576 mice with significant pre-existing Aβ loads, Aβ1-42 immunization only minimally decreased Aβ42 levels, whereas no alteration in Aβ40 levels or in plaque load was observed. These results indicate that in Tg2576 mice, Aβ1-42 immunization is more effective at preventing additional Aβ accumulation and does not result in significant clearance of pre-existing Aβ deposits.