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Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline

BACKGROUND: Fatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbance...

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Autores principales: González-Domínguez, Raúl, Castellano-Escuder, Pol, Lefèvre-Arbogast, Sophie, Low, Dorrain Y., Du Preez, Andrea, Ruigrok, Silvie R., Lee, Hyunah, Helmer, Catherine, Pallàs, Mercè, Urpi-Sarda, Mireia, Sánchez-Pla, Alex, Korosi, Aniko, Lucassen, Paul J., Aigner, Ludwig, Manach, Claudine, Thuret, Sandrine, Samieri, Cécilia, Andres-Lacueva, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725342/
https://www.ncbi.nlm.nih.gov/pubmed/34980257
http://dx.doi.org/10.1186/s13195-021-00948-8
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author González-Domínguez, Raúl
Castellano-Escuder, Pol
Lefèvre-Arbogast, Sophie
Low, Dorrain Y.
Du Preez, Andrea
Ruigrok, Silvie R.
Lee, Hyunah
Helmer, Catherine
Pallàs, Mercè
Urpi-Sarda, Mireia
Sánchez-Pla, Alex
Korosi, Aniko
Lucassen, Paul J.
Aigner, Ludwig
Manach, Claudine
Thuret, Sandrine
Samieri, Cécilia
Andres-Lacueva, Cristina
author_facet González-Domínguez, Raúl
Castellano-Escuder, Pol
Lefèvre-Arbogast, Sophie
Low, Dorrain Y.
Du Preez, Andrea
Ruigrok, Silvie R.
Lee, Hyunah
Helmer, Catherine
Pallàs, Mercè
Urpi-Sarda, Mireia
Sánchez-Pla, Alex
Korosi, Aniko
Lucassen, Paul J.
Aigner, Ludwig
Manach, Claudine
Thuret, Sandrine
Samieri, Cécilia
Andres-Lacueva, Cristina
author_sort González-Domínguez, Raúl
collection PubMed
description BACKGROUND: Fatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbances and common risk factors, namely the ɛ4 allele of the apolipoprotein E (ApoE-ɛ4) gene and sex, remains elusive. METHODS: In order to investigate early alterations associated with cognitive decline in the fatty acid-related serum metabolome, we here applied targeted metabolomics analysis on a nested case-control study (N=368), part of a prospective population cohort on dementia. RESULTS: When considering the entire study population, circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found to be increased among those participants who had greater odds of cognitive decline over a 12-year follow-up. Interestingly, stratified analyses indicated that these metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women. CONCLUSIONS: Altogether, our results highlight that the regulation of fatty acids and related metabolic pathways during ageing and cognitive decline depends on complex inter-relationships between the ApoE-ε4 genotype and sex. A better understanding of the ApoE-ɛ4 and sex dependent modulation of metabolism is essential to elucidate the individual variability in the onset of cognitive decline, which would help develop personalized therapeutic approaches. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00948-8.
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spelling pubmed-87253422022-01-06 Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline González-Domínguez, Raúl Castellano-Escuder, Pol Lefèvre-Arbogast, Sophie Low, Dorrain Y. Du Preez, Andrea Ruigrok, Silvie R. Lee, Hyunah Helmer, Catherine Pallàs, Mercè Urpi-Sarda, Mireia Sánchez-Pla, Alex Korosi, Aniko Lucassen, Paul J. Aigner, Ludwig Manach, Claudine Thuret, Sandrine Samieri, Cécilia Andres-Lacueva, Cristina Alzheimers Res Ther Research BACKGROUND: Fatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbances and common risk factors, namely the ɛ4 allele of the apolipoprotein E (ApoE-ɛ4) gene and sex, remains elusive. METHODS: In order to investigate early alterations associated with cognitive decline in the fatty acid-related serum metabolome, we here applied targeted metabolomics analysis on a nested case-control study (N=368), part of a prospective population cohort on dementia. RESULTS: When considering the entire study population, circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found to be increased among those participants who had greater odds of cognitive decline over a 12-year follow-up. Interestingly, stratified analyses indicated that these metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women. CONCLUSIONS: Altogether, our results highlight that the regulation of fatty acids and related metabolic pathways during ageing and cognitive decline depends on complex inter-relationships between the ApoE-ε4 genotype and sex. A better understanding of the ApoE-ɛ4 and sex dependent modulation of metabolism is essential to elucidate the individual variability in the onset of cognitive decline, which would help develop personalized therapeutic approaches. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00948-8. BioMed Central 2022-01-03 /pmc/articles/PMC8725342/ /pubmed/34980257 http://dx.doi.org/10.1186/s13195-021-00948-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
González-Domínguez, Raúl
Castellano-Escuder, Pol
Lefèvre-Arbogast, Sophie
Low, Dorrain Y.
Du Preez, Andrea
Ruigrok, Silvie R.
Lee, Hyunah
Helmer, Catherine
Pallàs, Mercè
Urpi-Sarda, Mireia
Sánchez-Pla, Alex
Korosi, Aniko
Lucassen, Paul J.
Aigner, Ludwig
Manach, Claudine
Thuret, Sandrine
Samieri, Cécilia
Andres-Lacueva, Cristina
Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline
title Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline
title_full Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline
title_fullStr Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline
title_full_unstemmed Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline
title_short Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline
title_sort apolipoprotein e and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725342/
https://www.ncbi.nlm.nih.gov/pubmed/34980257
http://dx.doi.org/10.1186/s13195-021-00948-8
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