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

被引:139
作者
Das, P [1 ]
Murphy, MP [1 ]
Younkin, LH [1 ]
Younkin, SG [1 ]
Golde, TE [1 ]
机构
[1] Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA
关键词
A beta vaccination; A beta 40; A beta 42; Tg2576; mice; Alzheimer's disease; amyloid plaques;
D O I
10.1016/S0197-4580(01)00245-7
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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.
引用
收藏
页码:721 / 727
页数:7
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