RESUMO
High homocysteine (Hcy) levels, mainly caused by vitamin B12 deficiency, have been reported to induce amyloid-ß (Aß) formation and tau hyperphosphorylation in mouse models of Alzheimer's disease. However, the relationship between B12 deficiency and Aß aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic C. elegans strain GMC101, which expresses human Aß1-42 peptides in muscle cells, to investigate the effects of B12 deficiency on Aß aggregation-associated paralysis. C. elegans GMC101 was grown on nematode growth medium with or without B12 supplementation or with 2-O-α-D-glucopyranosyl-L-ascorbic acid (AsA-2G) supplementation. The worms were age-synchronized by hypochlorite bleaching and incubated at 20 °C. After the worms reached the young adult stage, the temperature was increased to 25 °C to induce Aß production. Worms lacking B12 supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B12-deficient growth medium with AsA-2G rescued the paralysis phenotype. However, AsA-2G had no effect on the aggregation of Aß peptides. Our results indicated that B12 supplementation lowered Hcy levels and alleviated Aß toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aß toxicity.