Amyloid-beta (Aβ) cleaved from amyloid precursor protein (APP) has been proposed to play a central and causative role in the aetiology of Alzheimer's disease (AD). APP_swe/PSEN1_dE9 (APP/PS1) transgenic mice display chronic Aβ accumulation and deposition in the brain. L-arginine is a semi-essential amino acid with a number of bioactive metabolites, and altered arginine metabolism has been implicated in the pathogenesis and/or the development of AD. This study systematically investigated how arginine metabolic profiles changed in the frontal cortex, hippocampus, parahippocampal region and cerebellum of male APP/PS1 mice at 4, 9 and 17 months of age relative to their sex- and age-matched wildtype controls. Immunohistochemistry demonstrated age-related Aβ deposition in the brain. High-performance liquid chromatography and mass spectrometry revealed age-related increases in glutamine, spermidine and spermine in APP/PS1 mice in a region-specific manner. Notably, genotype-related increases in spermine were found in the frontal cortex at the 9-month age point and in the frontal cortex, hippocampus and parahippocampal region at 17 months of age. Given the existing literature indicating the role of polyamines (spermine in particular) in modulating the aggregation and toxicity of Aβ oligomers, increased spermidine and spermine levels in APP/PS1 mice may be a neuroprotective mechanism to combat Aβ toxicity. Future research is required to better understand the functional significance of these changes.

已提出从淀粉样前体蛋白 (APP) 切割下来的淀粉样蛋白-β (Aβ) 在阿尔茨海默病 (AD) 的病因学中起重要作用。APP _swe /PSEN1 _dE9(APP/PS1) 转基因小鼠在大脑中表现出慢性 Aβ 积累和沉积。L-精氨酸是一种半必需氨基酸，具有多种生物活性代谢物，精氨酸代谢的改变与 AD 的发病机制和/或发展有关。本研究系统地研究了 4、9 和 17 个月大的雄性 APP/PS1 小鼠的额叶皮层、海马、海马旁区和小脑中的精氨酸代谢谱相对于其性别和年龄匹配的野生型对照是如何变化的。免疫组织化学证明大脑中与年龄相关的 Aβ 沉积。高效液相色谱法和质谱法揭示了 APP/PS1 小鼠中谷氨酰胺、亚精胺和精胺的年龄相关性以区域特异性方式增加。尤其，在 9 个月大的额叶皮层和 17 个月大的额叶皮层、海马和海马旁区域发现了与基因型相关的精胺增加。鉴于现有文献表明多胺（特别是精胺）在调节 Aβ 寡聚体的聚集和毒性方面的作用，APP/PS1 小鼠中亚精胺和精胺水平的增加可能是对抗 Aβ 毒性的神经保护机制。未来的研究需要更好地理解这些变化的功能意义。APP/PS1 小鼠中亚精胺和精胺水平的增加可能是对抗 Aβ 毒性的神经保护机制。未来的研究需要更好地理解这些变化的功能意义。APP/PS1 小鼠中亚精胺和精胺水平的增加可能是对抗 Aβ 毒性的神经保护机制。未来的研究需要更好地理解这些变化的功能意义。