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Scientific article
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English

Sex-Specific Metabolic Pathways Were Associated with Alzheimer's Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort

Published inBiomedicines, vol. 9, no. 11, 1610
Publication date2021-11-03
First online date2021-11-03
Abstract

Background: physiological differences between males and females could contribute to the development of Alzheimer's Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives.

Methods: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cerebrospinal fluid (CSF) biomarkers, brain imaging, and cognition using regression analyses for 695 participants (377 females), followed by sex-specific pathway overrepresentation analyses,APOEε4 stratification and assessment of metabolites' discriminatory performance in AD.

Results: In females with AD, vanillylmandelate (tyrosine pathway) was increased and tryptophan betaine (tryptophan pathway) was decreased. The inclusion of these two metabolites (area under curve (AUC) = 0.83, standard error (SE) = 0.029) to a baseline model (covariates + CSF biomarkers, AUC = 0.92, SE = 0.019) resulted in a significantly higher AUC of 0.96 (SE = 0.012). Kynurenate was decreased in males with AD (AUC = 0.679, SE = 0.046).

Conclusions: metabolic sex-specific differences were reported, covering neurotransmission and inflammation pathways with AD endophenotypes. Two metabolites, in pathways related to dopamine and serotonin, were associated to females, paving the way to personalised treatment.

eng
Keywords
  • Alzheimer’s disease
  • Blood
  • Metabolic pathway
  • Metabolomics
  • Sex
  • Tryptophan betaine
  • Vanillylmandelate
Funding
  • European Commission - European Medical Information Framework [115372]
  • European Commission - European Prevention of Alzheimer’s Dementia Consortium [115736]
  • European Commission - Data-driven models for Progression Of Neurological Disease [666992]
Citation (ISO format)
XU, Jin et al. Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort. In: Biomedicines, 2021, vol. 9, n° 11, p. 1610. doi: 10.3390/biomedicines9111610
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Identifiers
ISSN of the journal2227-9059
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Creation11/16/2022 12:03:18 PM
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