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

Vaccinations with A beta1-42 have been shown to reduce amyloid burden in transgenic models of Alzheimer's disease (AD). We have further tested the efficacy of A beta1-42 immunization in the Tg2576 mouse model of AD by immunizing one group of mice with minimal A beta deposition, one group of mice with modest A beta deposition, and one group with significant A beta deposition. The effects of immunization on A beta deposition were examined using biochemical and immunohistochemical methods. In Tg2576 mice immunized prior to significant amyloid deposition, A beta1-42 immunization was highly effective. Biochemically extracted A beta 40 and A beta 42 levels were significantly reduced and immunohistochemical plaque load was also reduced. Immunization of mice with modest amounts of pre-existing A beta deposits selectively reduced A beta 42 without altering A beta 40, although plaque load was reduced. In contrast, in Tg2576 mice with significant pre-existing A beta loads, A beta1-42 immunization only minimally decreased A beta 42 levels, whereas no alteration in A beta 40 levels or in plaque load was observed. These results indicate that in Tg2576 mice, A beta1-42 immunization is more effective at preventing additional A beta accumulation and does not result in significant clearance of pre-existing A beta deposits. (C) 2001 Elsevier Science Inc. All rights reserved.