Alzheimer's disease (AD) is an aging-related neurodegenerative disorder. It is characterized clinically by progressive memory loss and impaired cognitive function. Its progression occurs from neuronal synapse loss to amyloid pathology and Tau deposit which eventually leads to the compromised neuronal function. Neurons in central nervous tissue work in a composite and intricate network with the glia and vascular cells. Microglia and astrocytes are becoming the prime focus due to their involvement in various aspects of neurophysiology, such as trophic support to neurons, synaptic modulation, and brain surveillance. AD is also often considered as the sequela of prolonged metabolic dyshomeostasis. The neuron and glia have different metabolic profiles as cytosolic glycolysis and mitochondrial-dependent oxidative phosphorylation (OXPHOS), especially under dyshomeostasis or with aging pertaining to their unique genetic built-up. Various efforts are being put in to decipher the role of mitochondrial dynamics regarding their trafficking, fission/fusion imbalance, and mitophagy spanning over both neurons and glia to improve aging-related brain health. The mitochondrial dysfunction may lead to activation in various signaling mechanisms causing metabolic reprogramming in glia cells, further accelerating AD-related pathogenic events. The glycolytic-dominant astrocytes switch to the neurotoxic phenotype, i.e., disease-associated astrocyte under metabolic stress. The microglia also transform from resting to reactive phenotype, i.e., disease-associated microglia. It may also exist in otherwise a misconception an M1, glycolytic, or M2, an OXPHOS-dependent phenotype. Further, glial transformation plays a vital role in regulating hallmarks of AD pathologies like synapse maintenance, amyloid, and Tau clearance. In this updated review, we have tried to emphasize the metabolic regulation of glial reactivity, mitochondrial quality control mechanisms, and their neuroinflammatory response in Alzheimer’s progression.

阿尔茨海默病 (AD) 是一种与衰老相关的神经退行性疾病。它的临床特征是进行性记忆丧失和认知功能受损。它的进展从神经元突触丧失到淀粉样蛋白病理和 Tau 沉积，最终导致神经元功能受损。中枢神经组织中的神经元与神经胶质细胞和血管细胞在一个复杂而复杂的网络中工作。由于小胶质细胞和星形胶质细胞参与神经生理学的各个方面，例如对神经元的营养支持、突触调节和大脑监测，它们正成为主要关注点。AD 也经常被认为是长期代谢失调的后遗症。神经元和神经胶质细胞具有不同的代谢特征，如胞质糖酵解和线粒体依赖性氧化磷酸化 (OXPHOS)，尤其是在与他们独特的基因组成有关的失衡或老化的情况下。正在进行各种努力来破译线粒体动力学在其运输、裂变/融合失衡以及跨越神经元和神经胶质细胞的线粒体自噬方面的作用，以改善与衰老相关的大脑健康。线粒体功能障碍可能导致各种信号机制的激活，从而导致神经胶质细胞中的代谢重编程，进一步加速与 AD 相关的致病事件。以糖酵解为主的星形胶质细胞转变为神经毒性表型，即在代谢压力下与疾病相关的星形胶质细胞。小胶质细胞也从静息转变为反应性表型，即疾病相关的小胶质细胞。它也可能存在于其他误解中，即 M1（糖酵解）或 M2（一种 OXPHOS 依赖性表型）。更远，胶质细胞转化在调节 AD 病理特征（如突触维持、淀粉样蛋白和 Tau 清除）中起着至关重要的作用。在这篇更新的综述中，我们试图强调神经胶质反应的代谢调节、线粒体质量控制机制以及它们在阿尔茨海默病进展中的神经炎症反应。