The apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for Alzheimer’s disease (AD). APOE4 carriers develop systemic metabolic dysfunction decades before showing AD symptoms. Accumulating evidence shows that the metabolic dysfunction accelerates AD development, including exacerbated amyloid-beta (Aβ) retention, neuroinflammation and cognitive decline. Therefore, preserving metabolic function early on may be critical to reducing the risk for AD. Here, we show that inulin increases beneficial microbiota and decreases harmful microbiota in the feces of young, asymptomatic APOE4 transgenic (E4FAD) mice and enhances metabolism in the cecum, periphery and brain, as demonstrated by increases in the levels of SCFAs, tryptophan-derived metabolites, bile acids, glycolytic metabolites and scyllo-inositol. We show that inulin also reduces inflammatory gene expression in the hippocampus. This knowledge can be utilized to design early precision nutrition intervention strategies that use a prebiotic diet to enhance systemic metabolism and may be useful for reducing AD risk in asymptomatic APOE4 carriers.
|Published - Aug 1 2019
Bibliographical noteFunding Information:
This research was supported by NIH grants R01AG054459 (funded by NIA and ODS), R01AG062480, NIH/CTSA grant UL1TR000117, and American Federation for Aging Research Grant #A12474 to A-LL and NIH/NIA R21AG058006 to JMM, and NIH/NIDDK Training Grant T32DK007778 to JDH and LMY. The 7T ClinScan small animal MRI scanner of the UK was funded by the S10 NIH Shared Instrumentation Program Grant (1S10RR029541-01). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health. SDM is employed by Metabolon Inc.. Metabolon Inc. provided support in the form of salary for author SDM but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2019 Hoffman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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