Lifelong immunization with human β-amyloid (1-42) protects Alzheimer's transgenic mice against cognitive impairment throughout aging
Lifelong immunization with human β-amyloid (1-42) protects Alzheimer's transgenic mice against cognitive impairment throughout aging
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DOI：
10.1016/j.neuroscience.2004.09.055
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Arendash, GW
中科院分区：
文献类型：
--
作者：
Jensen, MT;Mottin, MD;Arendash, GW
尽管主动和被动β淀粉样蛋白（Abeta）免疫疗法已被证明可以预防或减轻各种阿尔茨海默病转基因小鼠品系的认知障碍，但这些研究集中于单一任务并涉及标准统计分析。由于阿尔茨海默氏病影响多个认知领域，当前的研究采用了广泛的行为组合和多指标分析来确定成年期大部分时间（从 2-161/2 月龄）给予 APP+PS1 转基因小鼠的 Ap 免疫的影响。在成人（41/2-6 个月）和老年（15-161/2 个月）测试点，进行相同的 6 周行为电池测试。结果表明，AR 免疫疗法在两个测试点都部分或完全保护了 APP+PS1 小鼠，使其在跨越多个认知领域（参考学习/记忆、工作记忆、搜索/识别）的各种任务中的表现免受损害。在成人和老年测试点，即使通过判别功能分析对行为测量进行集体分析（作为“整体”表现），Ap 免疫疗法的认知益处也是显而易见的。由于在 15-161/2 个月测试点发生的行为保护没有 Abeta 沉积减少（或与之相关），因此 Abeta 免疫疗法的作用机制很可能涉及中和/去除大脑中的小 Abeta 寡聚物。然而，在这个老化测试点进行的因素分析中，大脑 Abeta 沉积测量值与关键认知测量值的负载相当大。总的来说，我们的结果表明，AR 沉积的整个过程会对认知能力产生有害影响，并且基于 Abeta 的预防策略可以提供长期的认知益处，一直延续到老年。 (C) 2005 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Although both active and passive betaamyloid (Abeta) immunotherapy have been shown to protect against or lessen cognitive impairment in various Alzheimer's transgenic mouse lines, these studies have focused on a single task and involved standard statistical analysis. Because Alzheimer's disease impacts multiple cognitive domains, the current study employed an extensive behavioral battery and multimetric analysis therein to determine the impact of Ap immunization given throughout most of adult life (from 2-161/2 months of age) to APP+PS1 transgenic mice. At both adult (41/2-6 month) and aged (15-161/2 month) test points, the same 6-week behavioral battery was administered. Results indicate that AR immunotherapy partially or completely protected APP+PS1 mice at both test points from otherwise impaired performance in a variety of tasks spanning multiple cognitive domains (reference learning/memory, working memory, search/recognition). At both adult and aged test points, the cognitive benefits of Ap immunotherapy were evident even when behavioral measures were analyzed collectively (as "overall" performance) through discriminant function analysis. Since behavioral protection at the 15-161/2 month test point occurred without a decrease in (or correlation to) Abeta deposition, the mechanism of Abeta immunotherapy's action most likely involves neutralization/removal of small Abeta oligomers from the brain. However, in factor analysis performed at this aged test point, brain Abeta deposition measures loaded heavily with key cognitive measures. Collectively, our results suggest that the entire process of AR deposition deleteriously impacts cognitive performance and that Abeta-based preventative strategies can provide long-term cognitive benefits extending well into older age. (C) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.