Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer's disease hallmarks.

Autor: Dave N; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA., Judd JM; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.; Arizona Alzheimer's Consortium, Phoenix, Arizona, USA., Decker A; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA., Winslow W; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA., Sarette P; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA., Villarreal Espinosa O; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA., Tallino S; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.; Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.; School of Life Sciences, Arizona State University, Tempe, Arizona, USA., Bartholomew SK; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.; Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.; School of Life Sciences, Arizona State University, Tempe, Arizona, USA., Bilal A; Translational Cardiovascular Research Center and Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA., Sandler J; Biosciences Mass Spectrometry Facility, Biodesign Institute, Arizona State University, Tempe, Arizona, USA., McDonough I; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA., Winstone JK; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.; Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.; School of Life Sciences, Arizona State University, Tempe, Arizona, USA., Blackwood EA; Translational Cardiovascular Research Center and Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA., Glembotski C; Translational Cardiovascular Research Center and Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA., Karr T; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.; Biosciences Mass Spectrometry Facility, Biodesign Institute, Arizona State University, Tempe, Arizona, USA., Velazquez R; Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.; Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.; School of Life Sciences, Arizona State University, Tempe, Arizona, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2023 Feb; Vol. 22 (2), pp. e13775. Date of Electronic Publication: 2023 Jan 15.
DOI: 10.1111/acel.13775
Abstrakt: There is an urgent need to identify modifiable environmental risk factors that reduce the incidence of Alzheimer's disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase protein in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. ~90% of Americans do not reach the recommended daily intake of dietary choline. Thus, it's imperative to determine whether dietary choline deficiency increases disease outcomes. Here, we placed 3xTg-AD, a model of AD, and non-transgenic (NonTg) control mice on either a standard laboratory diet with sufficient choline (ChN; 2.0 g/kg choline bitartrate) or a choline-deficient diet (Ch-; 0.0 g/kg choline bitartrate) from 3 to 12 (early to late adulthood) months of age. A Ch- diet reduced blood plasma choline levels, increased weight, and impaired both motor function and glucose metabolism in NonTg mice, with 3xTg-AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, elevated soluble and insoluble Amyloid-β and Thioflavin S structures, and tau hyperphosphorylation at various pathological epitopes in the hippocampus and cortex of 3xTg-AD Ch- mice. To gain mechanistic insight, we performed unbiased proteomics of hippocampal and blood plasma samples. Dietary choline deficiency altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, dietary choline deficiency altered protein networks associated with insulin metabolism, mitochondrial function, inflammation, and fructose metabolic processing. Our data highlight that dietary choline intake is necessary to prevent systems-wide organ pathology and reduce hallmark AD pathologies.
(© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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