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bioRxiv · 10.1101/2023.05.06.539713

Low circulating choline, a modifiable dietary factor, is associated with the pathological progression and metabolome dysfunction in Alzheimers disease.

Judd, J. M.·Jasbi, P.·Winslow, W.·Serrano, G. E.·Klein-Seetharaman, J.·Beach, T.·Velazquez, R.
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Abstract

Most Americans ([~]90%) are deficient in dietary choline, an essential nutrient. Associations between circulating choline and pathological progression in Alzheimers disease (AD) remain unknown. Here, we examined these associations and performed a metabolomic analysis in blood serum from severe AD, moderate AD, and healthy controls. Additionally, to gain mechanistic insight, we assessed the effects of dietary choline deficiency (Ch-) in 3xTg-AD mice and choline supplementation (Ch+) in APP/PS1 mice. In humans, we found AD-associated reductions in choline, its derivative acetylcholine (ACh), and elevated pro-inflammatory cytokine TNF. Choline and ACh were negatively correlated with Plaque density, Braak stage, and TNF, but positively correlated with MMSE and brain weight. Metabolites L-Valine, 4-Hydroxyphenylpyruvic, Methylmalonic, and Ferulic acids were associated with choline levels. In mice, Ch-paralleled AD severe, but Ch+ was protective. In conclusion, low circulating choline is associated with AD-neuropathological progression, illustrating the importance of dietary choline consumption to offset disease.

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Judd, J. M., Jasbi, P., Winslow, W., Serrano, G. E., Klein-Seetharaman, J., Beach, T., Velazquez, R.. 2023-05-08. Low circulating choline, a modifiable dietary factor, is associated with the pathological progression and metabolome dysfunction in Alzheimers disease.. https://doi.org/10.1101/2023.05.06.539713

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