The normal role of Alzheimer's disease (AD)-linked amyloid precursor protein (APP) in the brain remains incompletely understood. Previous studies have reported that lack of APP has detrimental effects on spines and electrophysiological parameters. APP has been described to be important in synaptic pruning during development. The effect of APP knockout on mature synapses is complicated by this role in development. We previously reported on differential changes in synaptic proteins and receptors in APP mutant AD transgenic compared to wild-type neurons, which revealed selective decreases in levels of pre- and post-synaptic proteins, including of surface glutamate receptors. In the present study, we undertook a similar analysis of synaptic composition but now in APP knockout compared to wild-type mouse neurons. Here we demonstrate alterations in levels of selective pre- and post-synaptic proteins and receptors in APP knockout compared to wild-type mouse primary neurons in culture and brains of mice in youth and adulthood. Remarkably, we demonstrate selective increases in levels of synaptic proteins, such as GluA1, in neurons with APP knockout and with RNAi knockdown, which tended to be opposite to the reductions seen in AD transgenic APP mutant compared to wild-type neurons. These data reinforce that APP is important for the normal composition of synapses.

阿尔茨海默氏病（AD）关联的淀粉样蛋白前体蛋白（APP）在大脑中的正常作用仍未完全了解。先前的研究报道，缺少APP对脊柱和电生理参数有不利影响。APP已被描述在发育过程中对突触修剪很重要。APP敲除对成熟突触的作用由于在发育中的这种作用而变得复杂。我们以前曾报道过与野生型神经元相比APP突变AD转基因中突触蛋白和受体的差异变化，这揭示了突触前和突触后蛋白（包括表面谷氨酸受体）水平的选择性降低。在本研究中，我们进行了类似的突触组成分析，但与野生型小鼠神经元相比，现在在APP敲除中。在这里，我们证明了与青年和成年小鼠的培养物和大脑中的野生型小鼠原代神经元相比，APP敲除中突触前和突触后蛋白质和受体水平的变化。值得注意的是，我们证明了具有APP敲除和RNAi敲除的神经元中突触蛋白（例如GluA1）水平的选择性增加，与野生型神经元相比，这倾向于与AD转基因APP突变体中的减少相反。这些数据表明APP对于突触的正常组成很重要。在具有APP敲除和RNAi敲除的神经元中，与野生型神经元相比，这与在AD转基因APP突变体中观察到的减少趋势相反。这些数据表明APP对于突触的正常组成很重要。在具有APP敲除和RNAi敲除的神经元中，与野生型神经元相比，这与在AD转基因APP突变体中观察到的减少趋势相反。这些数据表明APP对于突触的正常组成很重要。