abstract
- Alzheimer¿s disease (AD) is characterized by neurotoxic aggregation of amyloid-ß (Aß) peptides. We investigated the neuroprotective efficacy of docosahexaenoic acid (DHA) and dihydrocaffeic acid (DCA), individually and in combination, against Aß(1¿42)-induced toxicity in SH-SY5Y neuroblastoma cells. Exposure to 0.625 ¿M Aß for 24 h reduced cell viability by ~35%. Co-treatment with DHA or DCA (18.75¿37.5 ¿M) improved viability by 19¿26%, whereas higher doses were ineffective. The combination of DHA and DCA at 18.75 ¿M each yielded the greatest effect, restoring viability by ~ 32% and reducing Aß aggregation by ~36%, surpassing the effects of either compound alone. Fluorescence microscopy confirmed decreased Thioflavin T-positive aggregates in the combined treatment. These findings demonstrate that DHA and DCA exert complementary, additive neuroprotective effects and support their use as a multi-target nutraceutical strategy. This work highlights the potential of functional food formulations combining omega-3 fatty acids and polyphenol-derived metabolites for early-stage AD prevention. © 2025 The Author(s). Published with license by Taylor & Francis Group, LLC.