A REVIEW ON OXIDATIVE STRESS, NEUROINFLAMMATION, AND SYNAPTIC DYSFUNCTION IN ALZHEIMER'S DISEASE

Alzheimer’s disease (AD) is the most common form of dementia, contributing to nearly two-thirds of global cases and posing a major healthcare challenge. With over 55 million people currently affected, prevalence is expected to reach 139 million by 2050, accompanied by escalating social and economic burdens. Clinically, AD progresses gradually from subtle memory deficits to profound cognitive impairment, behavioral disturbances, complete dependency, and eventual death. Its neuropathological hallmarks include amyloid-β (Aβ) accumulation, tau hyperphosphorylation leading to neurofibrillary tangles, and extensive synaptic and neuronal loss. These features interact with secondary processes such as oxidative stress, chronic neuroinflammation, and mitochondrial dysfunction, which together accelerate neurodegeneration. Oxidative stress, driven by excessive reactive oxygen species (ROS) and mitochondrial failure, damages proteins, lipids, and DNA. Persistent activation of microglia and astrocytes promotes the release of pro-inflammatory cytokines, impairing amyloid clearance and amplifying neuronal injury. Synaptic dysfunction—the strongest correlate of cognitive decline—arises from Aβ- and tau-mediated toxicity, neurotransmitter imbalance, and excitotoxic signaling. Current treatments, including cholinesterase inhibitors and NMDA receptor antagonists, provide only symptomatic relief, while disease-modifying therapies against amyloid and tau show limited success. Promising approaches under investigation include antioxidant therapies, anti-inflammatory agents, synaptic repair strategies, and multi-target interventions addressing AD’s multifactorial pathology. Future progress will rely on sensitive biomarkers for early detection, precision medicine tailored to genetic and molecular risk factors, and improved translational models that better reflect human disease. A deeper mechanistic understanding of how oxidative stress, inflammation, and synaptic failure converge is vital for developing effective and transformative therapies for AD.