APOE ε4 and Alzheimer's disease diagnosis associated differences in L-carnitine, GBB, TMAO, and acylcarnitines in blood and brain.

Autor: Huguenard CJC; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA; Open University, Milton Keynes, UK., Cseresznye A; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA., Evans JE; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA., Darcey T; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA., Nkiliza A; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA; James A. Haley VA Hospital, Tampa, FL, USA., Keegan AP; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA., Luis C; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA., Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA., Arvanitakis Z; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA., Yassine HN; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Mullan M; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA; Open University, Milton Keynes, UK., Crawford F; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA; Open University, Milton Keynes, UK; James A. Haley VA Hospital, Tampa, FL, USA., Abdullah L; Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA; Open University, Milton Keynes, UK; James A. Haley VA Hospital, Tampa, FL, USA. Electronic address: labdullah@roskampinstitute.org.
Jazyk: angličtina
Zdroj: Current research in translational medicine [Curr Res Transl Med] 2023 Jan-Mar; Vol. 71 (1), pp. 103362. Date of Electronic Publication: 2022 Aug 11.
DOI: 10.1016/j.retram.2022.103362
Abstrakt: Background: The apolipoprotein E (APOE) ε4 allele, involved in fatty acid (FA) metabolism, is a major genetic risk factor for Alzheimer's disease (AD). This study examined the influence of APOE genotypes on blood and brain markers of the L-carnitine system, necessary for fatty acid oxidation (FAO), and their collective influence on the clinical and pathological outcomes of AD.
Methods: L-carnitine, its metabolites γ-butyrobetaine (GBB) and trimethylamine-n-oxide (TMAO), and its esters (acylcarnitines) were analyzed in blood from predominantly White community/clinic-based individuals (n = 372) and in plasma and brain from the Religious Order Study (ROS) (n = 79) using liquid chromatography tandem mass spectrometry (LC-MS/MS).
Findings: Relative to total blood acylcarnitines, levels of short chain acylcarnitines (SCAs) were higher whereas long chain acylcarnitines (LCAs) were lower in AD, which was observed pre-clinically in APOE ε4s. Plasma medium chain acylcarnitines (MCAs) were higher amongst cognitively healthy APOE ε2 carriers relative to other genotypes. Compared to their respective controls, elevated TMAO and lower L-carnitine and GBB were associated with AD clinical diagnosis and these differences were detected preclinically among APOE ε4 carriers. Plasma and brain GBB, TMAO, and acylcarnitines were also associated with post-mortem brain amyloid, tau, and cerebrovascular pathologies.
Interpretation: Alterations in blood L-carnitine, GBB, TMAO, and acylcarnitines occur early in clinical AD progression and are influenced by APOE genotype. These changes correlate with post-mortem brain AD and cerebrovascular pathologies. Additional studies are required to better understand the role of the FAO disturbances in AD.
Competing Interests: Declaration of Competing Interest The authors declare no competing interests.
(Copyright © 2022 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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