Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Alzheimer's Research and Therapy Année : 2022

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

Dorrain Y. Low
  • Fonction : Auteur
  • PersonId : 1130981
Claudine Manach

Résumé

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.
Fichier principal
Vignette du fichier
BPH_ART_2022_Gonzalez-Dominguez.pdf (936.04 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03597972 , version 1 (04-03-2022)

Licence

Paternité

Identifiants

Citer

Raul Gonzalez-Dominguez, Pol Castellano-Escuder, Sophie Lefevre Arbogast, Dorrain Y. Low, Andrea Du Preez, et al.. Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline. Alzheimer's Research and Therapy, 2022, 14, pp.1. ⟨10.1186/s13195-021-00948-8⟩. ⟨hal-03597972⟩
27 Consultations
22 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More