Alzheimer’s disease (AD) is the inoperable, incapacitating, neuropsychiatric, and degenerative manifestation that drastically affects human life quality. The current medications target extra-neuronal senile plaques, oxidative stress, neuroinflammation, intraneuronal neurofibrillary tangles, cholinergic deficits, and excitotoxicity. Among novel pathways and targets, bioenergetic and resultant mitochondrial dysfunction has been recognized as essential factors that decide the neuronal fate and consequent neurodegeneration in AD. The crucial attributes of mitochondria, including bioenergesis, signaling, sensing, integrating, and transmitting biological signals contribute to optimum networking of neuronal dynamics and make them indispensable for cell survival. In AD, mitochondrial dysfunction and mitophagy are a preliminary and critical event that aggravates the pathological cascade. Stress is known to promote and exaggerate the neuropathological alteration during neurodegeneration and metabolic impairments, especially in the cortico-limbic system, besides adversely affecting the normal physiology and mitochondrial dynamics. Stress involves the allocation of energy resources for neuronal survival. Chronic and aggravated stress response leads to excessive release of glucocorticoids by activation of the hypothalamic–pituitaryadrenal (HPA) axis. By acting through their receptors, glucocorticoids influence adverse mitochondrial changes and alter mtDNA transcription, mtRNA expression, hippocampal mitochondrial network, and ultimately mitochondrial physiology. Chronic stress also affects mitochondrial dynamics by changing metabolic and neuro-endocrinal signalling, aggravating oxidative stress, provoking inflammatory mediators, altering tropic factors, influencing gene expression, and modifying epigenetic pathways. Thus, exploring chronic stress-induced glucocorticoid dysregulation and resultant bio-behavioral and psychosomatic mitochondrial alterations may be a feasible narrative to investigate and unravel the mysterious pathobiology of AD.

阿尔茨海默病 (AD) 是一种无法手术、失能、神经精神和退化的表现，严重影响人类生活质量。目前的药物针对神经元外老年斑、氧化应激、神经炎症、神经元内神经原纤维缠结、胆碱能缺陷和兴奋性毒性。在新的途径和靶点中，生物能量和由此产生的线粒体功能障碍已被认为是决定 AD 中神经元命运和随之而来的神经变性的重要因素。线粒体的关键属性，包括生物能量、信号传导、传感、整合和传输生物信号，有助于神经元动力学的最佳网络化，并使它们对细胞生存不可或缺。在广告中，线粒体功能障碍和线粒体自噬是加剧病理级联反应的初步和关键事件。已知压力会促进和夸大神经变性和代谢损伤期间的神经病理学改变，尤其是在皮质边缘系统中，此外还会对正常生理学和线粒体动力学产生不利影响。压力涉及为神经元生存分配能量资源。慢性和加重的应激反应通​​过激活下丘脑-垂体肾上腺 (HPA) 轴导致糖皮质激素过度释放。通过其受体作用，糖皮质激素影响不利的线粒体变化并改变 mtDNA 转录、mtRNA 表达、海马线粒体网络，并最终改变线粒体生理学。慢性压力还通过改变代谢和神经内分泌信号、加重氧化应激、激发炎症介质、改变热带因子、影响基因表达和改变表观遗传途径来影响线粒体动力学。因此，探索慢性应激诱导的糖皮质激素失调以及由此产生的生物行为和心身线粒体改变可能是研究和解开 AD 神秘病理生物学的可行叙述。