Int J Immunopathol Pharmacol. 2012 Apr-Jun;25(2):345-53. doi: 10.1177/039463201202500204.
Alzheimer's disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The primary cause and sequence of its progression are only partially understood but abnormalities in folding and accumulation of insoluble proteins such as beta-amyloid and Tau-protein are both associated with the pathogenesis of AD. Mitochondria play a crucial role in cell survival and death, and changes in mitochondrial structure and/or function are related to many human diseases. Increasing evidence suggests that compromised mitochondrial function contributes to the aging process and thus may increase the risk of AD. Dysfunctional mitochondria contribute to reactive oxygen species which can lead to extensive macromolecule oxidative damage and the progression of amyloid pathology. Oxidative stress and amyloid toxicity leave neurons chemically vulnerable. The mitochondrial toxicity induced by beta-amyloid is still not clear but may include numerous mechanisms, such as the increased permeability of mitochondrial membranes, the disruption of calcium homeostasis, the alteration of oxidative phosphorylation with a consequent overproduction of reactive oxygen species. Other mechanisms have been associated with the pathophysiology of AD. Inflammatory changes are observed in AD brain overall, particularly at the amyloid deposits, which are rich in activated microglia. Once stimulated, the microglia release a wide variety of pro-inflammatory mediators including cytokines, complement components and free radicals, all of which potentially contribute to further neuronal dysfunction and eventually death. Clinically, novel approaches to visualize early neuroinflammation in the human brain are needed to improve the monitoring and control of therapeutic strategies that target inflammatory and other pathological mechanisms. Similarly, there is growing interest in developing agents that modulate mitochondrial function.
阿尔茨海默病（AD）是一种多因素紊乱，其特征是神经元网络的进行性恶化。其主要原因和进展顺序仅部分了解，但异常折叠和不溶性蛋白质的积累，如β-淀粉样蛋白和 Tau 蛋白都与 AD 的发病机制有关。线粒体在细胞存活和死亡中起着至关重要的作用，线粒体结构和/或功能的变化与许多人类疾病有关。越来越多的证据表明，受损的线粒体功能导致衰老过程，因此可能会增加 AD 的风险。功能失调的线粒体有助于产生活性氧，从而导致广泛的大分子氧化损伤和淀粉样蛋白病理的进展。氧化应激和淀粉样毒性使神经元在化学上变得脆弱。β-淀粉样蛋白诱导的线粒体毒性尚不清楚，但可能包括许多机制，如线粒体膜通透性增加、钙稳态破坏、氧化磷酸化改变以及随之而来的活性氧过度产生。其他机制与 AD 的病理生理学有关。在 AD 大脑中观察到整体炎症变化，特别是在富含活化小胶质细胞的淀粉样沉积处。一旦被刺激，小胶质细胞释放出多种促炎介质，包括细胞因子、补体成分和自由基，所有这些都可能导致进一步的神经元功能障碍并最终导致死亡。临床上，需要新的方法来可视化人类大脑中的早期神经炎症，以改善对靶向炎症和其他病理机制的治疗策略的监测和控制。同样，人们越来越有兴趣开发调节线粒体功能的药物。
