Huguenard, Claire J. C. and Cseresznye, Adam and Darcey, Teresa and Nkiliza, Aurore and Evans, James E. and Hazen, Stanley L. and Mullan, Michael and Crawford, Fiona and Abdullah, Laila (2023) Age and APOE affect L-carnitine system metabolites in the brain in the APOE-TR model. Frontiers in Aging Neuroscience, 14. ISSN 1663-4365
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Abstract
With age the apolipoprotein E (APOE) E4 allele (involved in lipid homeostasis) is associated with perturbation of bioenergetics pathways in Alzheimer’s disease (AD). We therefore hypothesized that in aging mice APOE genotype would affect the L-carnitine system (central to lipid bioenergetics), in the brain and in the periphery. Using liquid chromatography-mass spectrometry, levels of L-carnitine and associated metabolites: γ-butyrobetaine (GBB), crotonobetaine, as well as acylcarnitines, were evaluated at 10-, 25-, and 50-weeks, in the brain and the periphery, in a targeted replacement mouse model of human APOE (APOE-TR). Aged APOE-TR mice were also orally administered 125 mg/kg of L-carnitine daily for 7 days followed by evaluation of brain, liver, and plasma L-carnitine system metabolites. Compared to E4-TR, an age-dependent increase among E2- and E3-TR mice was detected for medium- and long-chain acylcarnitines (MCA and LCA, respectively) within the cerebrovasculature and brain parenchyma. While following L-carnitine oral challenge, E4-TR mice had higher increases in the L-carnitine metabolites, GBB and crotonobetaine in the brain and a reduction of plasma to brain total acylcarnitine ratios compared to other genotypes. These studies suggest that with aging, the presence of the E4 allele may contribute to alterations in the L-carnitine bioenergetic system and to the generation of L-carnitine metabolites that could have detrimental effects on the vascular system. Collectively the E4 allele and aging may therefore contribute to AD pathogenesis through aging-related lipid bioenergetics as well as cerebrovascular dysfunctions.
Item Type: | Article |
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Subjects: | STM Digital Press > Medical Science |
Depositing User: | Unnamed user with email support@stmdigipress.com |
Date Deposited: | 14 Apr 2023 09:24 |
Last Modified: | 25 Jul 2024 07:57 |
URI: | http://publications.articalerewriter.com/id/eprint/564 |