| Summary: | Medical therapies to avoid the progression of Alzheimer’s disease (AD) are limited to date. Certain diets have been associated with a lower incidence of neurodegenerative diseases. In particular, the regular intake of foods rich in polyphenols, such as epicatechin (EC), could help prevent or mitigate AD progression. This work aims to explore the neuroprotective effects of EC using different transgenic strains of <i>Caenorhabditis elegans</i>, which express human Aβ<sub>1-42</sub> peptides and contribute to elucidating the mechanisms involved in the effects of EC in AD. The performed assays indicate that this flavan-3-ol was able to reduce the signs of β-amyloid accumulation in <i>C. elegans</i>, improving motility and chemotaxis and increasing survival in transgenic strain peptide producers compared to nematodes not treated with EC. The neuroprotective effects exhibited by EC in <i>C. elegans</i> could be explained by the modulation of inflammation and stress-associated genes, as well as autophagy, microgliosis, and heat shock signaling pathways, involving the regulation of <i>cpr-5</i>, <i>epg-8</i>, <i>ced-7</i>, <i>ZC239.12</i>, and <i>hsp-16</i> genes. Overall, the results obtained in this study support the protective effects of epicatechin against Aβ-induced toxicity.
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