Reduced effectiveness of A beta 1-42 immunization in APP transgenic mice with significant amyloid deposition

Vaccinations with A beta1-42 have been shown to reduce amyloid burden in tr ansgenic models of Alzheimer's disease (AD). We have further tested the eff icacy of A beta1-42 immunization in the Tg2576 mouse model of AD by immuniz ing one group of mice with minimal A beta deposition, one group of mice wit h modest A beta deposition, and one group with significant A beta depositio n. The effects of immunization on A beta deposition were examined using bio chemical and immunohistochemical methods. In Tg2576 mice immunized prior to significant amyloid deposition, A beta1-42 immunization was highly effecti ve. Biochemically extracted A beta 40 and A beta 42 levels were significant ly reduced and immunohistochemical plaque load was also reduced. Immunizati on 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 redu ced. In contrast, in Tg2576 mice with significant pre-existing A beta loads , A beta1-42 immunization only minimally decreased A beta 42 levels, wherea s no alteration in A beta 40 levels or in plaque load was observed. These r esults indicate that in Tg2576 mice, A beta1-42 immunization is more effect ive at preventing additional A beta accumulation and does not result in sig nificant clearance of pre-existing A beta deposits. (C) 2001 Elsevier Scien ce Inc. All rights reserved.