Abstract
Alzheimer’s disease (AD), the most common cause of dementia, remains a major neurodegenerative disorder with an incompletely understood etiology despite decades of research. While beta-amyloid plaques and neurofibrillary tau tangles represent the defining pathological hallmarks of AD, growing evidence indicates that the disease’s progression is profoundly influenced by chronic neuroinflammation. Microglia and astrocytes, which are essential for maintaining neuronal homeostasis, clear plaques, support vascular and synaptic function, undergo a pathological shift in AD from protective regulators to dysfunctional, proinflammatory mediators. This transition is characterized by impaired plaque phagocytosis, excessive cytokine release, oxidative stress, and blood-brain barrier (BBB) disruption, all of which contribute to synaptic loss and neurodegeneration. However, the mechanisms driving glial failure remain poorly defined, leaving unresolved questions about whether neuroinflammation in AD acts as an amplifier of existing pathology or a downstream consequence. This literature review examines recent evidence on microglial and astrocytic dysfunction in AD, evaluates proposed cellular and molecular mechanisms underlying their pathological transformation, and explores the potential for glial-targeted interventions. Emerging research suggests that restoring glial function, rather than solely targeting plaques or tau tangles, may offer a promising strategy to slow or delay AD progression by enhancing plaque clearance, maintaining metabolic and vascular stability, and reducing inflammatory neurotoxicity.