Department of Anatomy, University of Otago, Dunedin, New Zealand.
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Transl Psychiatry. 2018 May 25;8(1):108. doi: 10.1038/s41398-018-0149-z.
While amyloid-beta (Aβ) peptides play a central role in the development of Alzheimer's disease (AD), recent evidence also implicates altered metabolism of L-arginine in the pathogenesis of AD. The present study systematically investigated how behavioural function and the brain and plasma arginine metabolic profiles changed in a chronic Aβ accumulation model using male APPswe/PS1ΔE9 transgenic (Tg) mice at 7 and 13 months of age. As compared to their wild-type (WT) littermates, Tg mice displayed age-related deficits in spatial water maze tasks and alterations in brain arginine metabolism. Interestingly, the plasma arginine metabolic profile was markedly altered in 7-month Tg mice prior to major behavioural impairment. Receiver operating characteristic curve analysis revealed that plasma putrescine and spermine significantly differentiated between Tg and WT mice. These results demonstrate the parallel development of altered brain arginine metabolism and behavioural deficits in Tg mice. The altered plasma arginine metabolic profile that preceded the behavioural and brain profile changes suggests that there may be merit in an arginine-centric set of ante-mortem biomarkers for AD.
虽然淀粉样蛋白-β（Aβ）肽在阿尔茨海默病（AD）的发展中起核心作用，但最近的证据也表明 L-精氨酸代谢的改变与 AD 的发病机制有关。本研究系统地研究了慢性 Aβ 积累模型中雄性 APPswe/PS1ΔE9 转基因（Tg）小鼠在 7 个月和 13 个月大时的行为功能以及大脑和血浆精氨酸代谢谱如何变化。与野生型（WT）同窝仔相比，Tg 小鼠在空间水迷宫任务中表现出与年龄相关的缺陷，并改变了大脑精氨酸代谢。有趣的是，在出现主要行为障碍之前，7 月龄 Tg 小鼠的血浆精氨酸代谢谱明显改变。受试者工作特征曲线分析显示，血浆腐胺和精脒可显著区分 Tg 和 WT 小鼠。这些结果表明，Tg 小鼠的大脑精氨酸代谢改变和行为缺陷平行发展。在行为和大脑图谱改变之前发生的改变的血浆精氨酸代谢谱表明，对于 AD 来说，以精氨酸为中心的一组生前生物标志物可能具有一定的价值。
