Abstract：
Apolipoprotein-E4 (ApoE4) is an important genetic risk factor for Alzheimer\'s disease. The development of targeted-replacement human ApoE knock-in mice facilitates research into mechanisms by which ApoE4 affects the brain. We performed meta-analyses and meta-regression analyses to examine differences in cognitive performance between ApoE4 and ApoE3 mice. We included 61 studies in which at least one of the following tests was assessed: Morris Water Maze (MWM), novel object location (NL), novel object recognition (NO) and Fear Conditioning (FC) test. ApoE4 vs. ApoE3 mice performed significantly worse on the MWM (several outcomes, 0.17 ≤ g ≤ 0.60), NO (exploration, g=0.33; index, g=0.44) and FC (contextual, g=0.49). ApoE4 vs. ApoE3 differences were not systematically related to sex or age. We conclude that ApoE4 knock-in mice in a non-AD condition show some, but limited cognitive deficits, regardless of sex and age. These effects suggest an intrinsic vulnerability in ApoE4 mice that may become more pronounced under additional brain load, as seen in neurodegenerative diseases.
摘要：
载脂蛋白E4(ApoE4)是阿尔茨海默病的重要遗传危险因素。靶向替代人类ApoE敲入小鼠的发展促进了对ApoE4影响大脑机制的研究。我们进行了荟萃分析和荟萃回归分析，以检查ApoE4和ApoE3小鼠之间认知表现的差异。我们纳入了61项研究，其中至少评估了以下测试之一：莫里斯水迷宫（MWM），新对象位置(NL)，新颖的物体识别(NO)和恐惧条件(FC)测试。ApoE4vs.ApoE3小鼠在MWM上的表现明显更差(几个结果，0.17≤g≤0.60)，否(探索，g=0.33；指数，g=0.44)和FC(上下文，g=0.49)。ApoE4vs.ApoE3差异与性别或年龄无关。我们得出结论，ApoE4敲入小鼠在非AD条件下显示一些，但是有限的认知缺陷，不分性别和年龄。这些影响表明ApoE4小鼠的内在脆弱性在额外的脑负荷下可能变得更加明显。如在神经退行性疾病中看到的。
