Effects of Vitamin B(12) Deficiency on Amyloid-β Toxicity in Caenorhabditis elegans

High homocysteine (Hcy) levels, mainly caused by vitamin B(12) deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B(12) deficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic C. elegans strain GMC101, which expresses human Aβ(1–42) peptides in muscle cells, to investigate the effects of B(12) deficiency on Aβ aggregation–associated paralysis. C. elegans GMC101 was grown on nematode growth medium with or without B(12) 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 Aβ production. Worms lacking B(12) supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B(12)-deficient growth medium with AsA-2G rescued the paralysis phenotype. However, AsA-2G had no effect on the aggregation of Aβ peptides. Our results indicated that B(12) supplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity.