Extracellular Vesicles in Alzheimer’s Disease: Mechanisms, Immunotherapy Links, and Clinical Translation

Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction, neuroinflammation, and cognitive impairment. Although amyloid-β and tau continue to serve as core biomarkers and therapeutic targets, the clinical efficacy of recent biologic agents targeting amyloid has led to a new paradigm in AD treatment. Nevertheless, emerging data show that lipid metabolism is an important and well-established aspect of AD pathophysiology rather than a new theory. Lipid processing in microglia, astrocytes, and neurons is disrupted, leading to chronic inflammation, impaired amyloid clearance, mitochondrial dysfunction, and synaptic dysfunction. This review critically analyzes how lipid accumulation and lipid droplet biology contribute to Alzheimer's disease using cellular, animal, and human studies. Special focus is placed on enzymatic regulators such as DGAT2, cholesterol transport, and neuron–glia metabolic linkages. This review synthesizes existing mechanistic and translational data to emphasize lipid dysregulation as a complementary therapeutic target and potential biomarker axis that may improve current amyloid- and taudirected therapeutic strategies.