Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Perth, WA, Australia.
J Alzheimers Dis. 2011;25(3):433-44. doi: 10.3233/JAD-2011-101944.
The E4 allele of the apolipoprotein E (ApoE) gene has been identified as a major risk factor for the development of late onset Alzheimer's disease (AD). However, the mechanisms by which this gene affects AD are not fully understood. Studies of ApoE knock-out (ApoE KO) mice have revealed an exacerbation of two major pathologies that are diagnostic of AD: neurofibrillary tangles and senile plaques. However, evidence as to whether these mice have cognitive deficits is not yet conclusive. This ambiguity may arise partly from confounds associated with reliance on limited memory models, primarily, the Morris water maze task. An 8-arm radial maze task was therefore used to measure spatial memory in the ApoE KO mice, compared to controls over time. Furthermore, the effectiveness of a combination antioxidant therapy (CAT), designed to slow down the progression of AD based on concepts of oxidative stress and inflammatory processes underlying the pathology, was tested on memory ability. A significant strain difference was observed with the ApoE KO mice performing better than controls in terms of reference memory and corrects entries. No significant strain difference was observed for performance in terms of working memory errors. No significant effect of the CAT supplementation was observed.
载脂蛋白 E（ApoE）基因的 E4 等位基因已被确定为晚期发病阿尔茨海默病（AD）的主要危险因素。然而，该基因影响 AD 的机制尚不完全清楚。对载脂蛋白 E 敲除（ApoE KO）小鼠的研究揭示了两种主要病理的加重，这是 AD 的诊断特征：神经纤维缠结和老年斑。然而，这些小鼠是否存在认知缺陷的证据尚不确定。这种模糊性可能部分源于对有限记忆模型的依赖的混淆，主要是 Morris 水迷宫任务。因此，使用 8 臂放射状迷宫任务来测量 ApoE KO 小鼠的空间记忆，随着时间的推移与对照进行比较。此外，还测试了一种旨在基于氧化应激和炎症过程概念减缓 AD 进展的组合抗氧化治疗（CAT）对记忆能力的有效性。观察到 ApoE KO 小鼠与对照组之间存在显著的品系差异，ApoE KO 小鼠在参考记忆和正确进入方面表现更好。在工作记忆错误方面，未观察到性能的显著品系差异。未观察到 CAT 补充的显著效果。
