bioRxiv Neuroscience
bioRxiv Neuroscience
Preprint
2 years ago

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

Nikhil Dave, Jessica M Judd, Annika Decker, Wendy Winslow, Patrick Sarette, Oscar V Espinosa, Jessica A Sandler, Alina Bilal, Savannah Tallino, Ian McDonough, Erik Blackwood, Christopher Glembotski, Timothy Karr, Ramon Velazquez
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 do not reach the recommended daily choline intake. Thus, it is 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.

Publisher URL: https://www.biorxiv.org/content/10.1101/2022.08.14.503929v1

DOI: 10.1101/2022.08.14.503929

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