Department of Human Movement Sciences, University of Groningen, University Medical Center Groningen, Groningen, A. Deusinglaan 1, Groningen 9713AV, the Netherlands.
Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborg 7, Groningen 9747 AG, the Netherlands; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, Edegem 2650, Belgium.
Behav Brain Res. 2024 Aug 5;471:115123. doi: 10.1016/j.bbr.2024.115123. Epub 2024 Jul 6.
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.
载脂蛋白 E4（ApoE4）是阿尔茨海默病的重要遗传风险因素。靶向替换人类 ApoE 基因敲入小鼠的发展促进了研究 ApoE4 如何影响大脑的机制。我们进行了荟萃分析和荟萃回归分析，以检查 ApoE4 和 ApoE3 小鼠在认知表现上的差异。我们纳入了至少评估了以下测试之一的 61 项研究：Morris 水迷宫（MWM）、新物体位置（NL）、新物体识别（NO）和恐惧条件反射（FC）测试。与 ApoE3 相比，ApoE4 小鼠在 MWM（几种结果，0.17 ≤ g ≤ 0.60）、NO（探索，g=0.33；指数，g=0.44）和 FC（语境，g=0.49）上的表现明显更差。ApoE4 与 ApoE3 的差异与性别或年龄没有系统的关系。我们得出结论，在非 AD 条件下，ApoE4 基因敲入小鼠表现出一些认知缺陷，但有限，无论性别和年龄如何。这些影响表明 ApoE4 小鼠存在内在的脆弱性，在额外的大脑负荷下可能会更加明显，如在神经退行性疾病中所见。
