Vitamin B-12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no effective treatment. Diet, as a modifiable risk factor for AD, could potentially be targeted to slow disease onset and progression. However, complexity of the human diet and indirect effects of the microbiome make it challenging to identify protective nutrients. Multiple factors contribute to AD pathogenesis, including amyloid beta (Ab) deposition, energy crisis, and oxidative stress. Here, we use Caenorhabditis elegans to define the impact of diet on Ab proteotoxicity. We discover that dietary vitamin B-12 alleviates mitochondrial fragmentation, bioenergetic defects, and oxidative stress, delaying Ab-induced paralysis without affecting Ab accumulation. Vitamin B-12 has this protective effect by acting as a cofactor for methionine synthase, impacting the methionine/S-adenosylmethionine (SAMe) cycle. Vitamin B-12 supplementation of B-12-deficient adult Ab animals is beneficial, demonstrating potential for vitamin B-12 as a therapy to target pathogenic features of AD triggered by proteotoxic stress.

Automated summary

The study found that dietary vitamin B-12 can alleviate mitochondrial fragmentation, bioenergetic defects, and oxidative stress caused by Ab proteotoxicity, delaying the onset of the disease. Vitamin B-12 acts as a cofactor for methionine synthase, impacting the methionine/S-adenosylmethionine (SAMe) cycle, showing potential as a therapy to target pathogenic features of AD.