Wang Jun, Ikonen Sami, Gurevicius Kestutis, van Groen Thomas, Tanila Heikki
Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.
Brain Res. 2002 Jul 12;943(2):181-90. doi: 10.1016/s0006-8993(02)02617-3.
Transgenic mice expressing human APPswe and PS1-A264E mutations mimic certain neuropathological features of Alzheimer's disease (AD). These mice have elevated levels of the highly fibrillogenic amyloid beta1-42 peptide (Abeta42) and develop amyloid plaques around the age of 9 months. Our aim was to find whether these transgenic mice differ electrophysiologically from non-transgenic mice and whether the alteration in EEG activity progresses with the accumulation of Abeta. The APP/PS1 mice had reduced cortical theta activity and enhanced beta and gamma activity, but these changes were not age-dependent. APP single mutant mice had similar EEG alterations in theta, beta and gamma bands as APP/PS1 double mutant mice while PS1 single mutant mice did not differ from non-transgenic controls. Insoluble Abeta40 and Abeta42 levels were robustly increased in APP/PS1 double mutant mice and insoluble Abeta40 moderately increased also in APP single mutant mice. Soluble Abeta42 was found in all APP mutant mice but also in lower concentrations in PS1 single mutant mice. Plaques were deposited in 13-month-old APP/PS1 double mutant mice but not in 8-month-old double mutant or 13-month-old single mutant mice. We conclude that the alteration of EEG activity in APP/PS1 double mutant and APP single mutant mice is related to their APP genotype rather than to deposition of beta-amyloid in the brain.
表达人APPswe和PS1 - A264E突变的转基因小鼠模拟了阿尔茨海默病（AD）的某些神经病理学特征。这些小鼠中高度纤维化的淀粉样β1 - 42肽（Abeta42）水平升高，并在9个月龄左右出现淀粉样斑块。我们的目的是研究这些转基因小鼠在电生理方面是否与非转基因小鼠不同，以及脑电图（EEG）活动的改变是否随着Abeta的积累而进展。APP/PS1小鼠的皮质θ活动降低，β和γ活动增强，但这些变化与年龄无关。APP单突变小鼠在θ、β和γ频段的脑电图改变与APP/PS1双突变小鼠相似，而PS1单突变小鼠与非转基因对照无差异。APP/PS1双突变小鼠中不溶性Abeta40和Abeta42水平显著升高，APP单突变小鼠中不溶性Abeta40也适度升高。在所有APP突变小鼠中均发现可溶性Abeta42，但在PS1单突变小鼠中浓度较低。在13月龄的APP/PS1双突变小鼠中出现斑块，但在8月龄双突变小鼠或13月龄单突变小鼠中未出现。我们得出结论，APP/PS1双突变小鼠和APP单突变小鼠的EEG活动改变与其APP基因型有关，而非与脑中β淀粉样蛋白的沉积有关。
