Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimers disease hallmarks

Dave, N.; Judd, J. M.; Decker, A.; Winslow, W.; Sarette, P.; Espinosa, O. V.; Sandler, J. A.; Bilal, A.; Tallino, S.; McDonough, I.; Blackwood, E.; Glembotski, C.; Karr, T.; Velazquez, R.

doi:10.1101/2022.08.14.503929

bioRxiv · 10.1101/2022.08.14.503929

Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimers disease hallmarks

Dave, N.·Judd, J. M.·Decker, A.·Winslow, W.·Sarette, P.·Espinosa, O. V.·Sandler, J. A.·Bilal, A.·Tallino, S.·McDonough, I.·Blackwood, E.·Glembotski, C.·Karr, T.·Velazquez, R.

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Abstract

Evidence suggests that environmental factors may contribute to Alzheimers disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase (PEMT) enzyme in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. [~]90% of Americans dont reach the recommended daily choline intake. Thus, its imperative to determine whether dietary deficiency increases disease outcomes. Here, we placed 3xTg-AD, a model of AD, and non-transgenic (NonTg) control mice on either a sufficient choline (ChN) or choline deficient (Ch-; choline deficiency) diet from 3 to 12 (early to late adulthood) months of age. Ch- reduced plasma choline and acetylcholine levels, increased weight, and impaired both glucose metabolism and motor function in NonTg, with 3xTg-AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, and elevated Amyloid-{beta} and phosphorylated tau in the hippocampus and cortex of 3xTg-AD Ch- mice. Unbiased proteomic analyses revealed Ch- altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, Ch- altered protein networks associated with insulin metabolism, mitochondrial function, and inflammation. Collectively, our data highlight that dietary choline intake is necessary to prevent systems-wide organ pathology and reduce AD hallmark pathologies.

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Dave, N., Judd, J. M., Decker, A., Winslow, W., Sarette, P., Espinosa, O. V., Sandler, J. A., Bilal, A., Tallino, S., McDonough, I., Blackwood, E., Glembotski, C., Karr, T., Velazquez, R.. 2022-08-15. Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimers disease hallmarks. https://doi.org/10.1101/2022.08.14.503929

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