Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease: Insights into Pathophysiology and Treatment

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily marked by cognitive decline and memory loss. Oxidative stress (OS) has emerged as a critical factor in AD pathogenesis, contributing to hallmark features such as amyloid-β (Aβ) plaque formation, tau hyperphosphorylation, and synaptic dysfunction. This review delves into the complex mechanisms driving reactive oxygen species (ROS) production, including mitochondrial dysfunction, metal ion dysregulation, and impaired antioxidant defenses, and examines their damaging effects on neuronal integrity. Elevated ROS levels in the aging brain cause oxidative modifications to lipids, proteins, and DNA, leading to neuronal atrophy, synapse loss, and cognitive impairment. Mitochondrial dysfunction amplifies OS by disrupting cellular energy metabolism and further promoting neurodegeneration through excessive ROS generation and reduced ATP production. Despite strong evidence linking OS to AD, clinical trials with antioxidant therapies have yielded inconsistent results. However, emerging therapeutic strategies, including targeted mitochondrial antioxidants and combination therapies, offer promising avenues for mitigating OS-related damage. This review emphasizes the need for a multifaceted therapeutic approach to address the complexity of OS in AD, with the goal of developing more effective treatments and improving patient outcomes.