Docosahexaenoic acid (DHA), an omega-3 fatty acid found in marine sources, has gained attention for its potential therapeutic role in Alzheimer’s disease (AD). This review systematically examines evidence from clinical studies and preclinical models regarding the potential of DHA to enhance cognitive function and protect against neurodegeneration linked to AD.

DHA modulates inflammatory pathways, potentially reducing neuroinflammation associated with AD, and its antioxidant properties may help mitigate oxidative stress, a critical factor in neuronal degeneration.

DHA has been reported to reduce neuroinflammatory mediators, enhance antioxidant enzyme activity, and stabilize neuronal membrane fluidity. It promotes synaptic plasticity through the upregulation of NMDA receptor subunits (NR2A/NR2B), tropomyosin receptor kinase B (TrkB), brain-derived neurotrophic factor (BDNF), synaptophysin, and postsynaptic density protein-95 (PSD-95), and enhances neurogenesis in the dentate gyrus. DHA has been associated with improvements in learning, memory performance, and various markers of neuronal function. However, variability across studies – including differences in DHA source, dosage, duration, and study design – affects the consistency of observed outcomes.

DHA may exert multiple neuroprotective actions relevant to AD, including anti-inflammatory, antioxidant, membrane-modulating, and synaptic-supportive effects. These mechanisms may contribute to improvements in cognitive and neuronal outcomes. Combining DHA with other therapeutic agents – antioxidants and anti-inflammatory drugs – represents a potential approach to AD treatment.