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

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

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 w...

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Autores principales: Jin Xu, Rebecca Green, Min Kim, Jodie Lord, Amera Ebshiana, Sarah Westwood, Alison L. Baird, Alejo J. Nevado-Holgado, Liu Shi, Abdul Hye, Stuart G. Snowden, Isabelle Bos, Stephanie J. B. Vos, Rik Vandenberghe, Charlotte E. Teunissen, Mara Ten Kate, Philip Scheltens, Silvy Gabel, Karen Meersmans, Olivier Blin, Jill Richardson, Ellen Elisa De Roeck, Sebastiaan Engelborghs, Kristel Sleegers, Régis Bordet, Lorena Rami, Petronella Kettunen, Magda Tsolaki, Frans R. J. Verhey, Daniel Alcolea, Alberto Lleó, Gwendoline Peyratout, Mikel Tainta, Peter Johannsen, Yvonne Freund-Levi, Lutz Frölich, Valerija Dobricic, Giovanni B. Frisoni, José Luis Molinuevo, Anders Wallin, Julius Popp, Pablo Martinez-Lage, Lars Bertram, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Pieter Jelle Visser, Simon Lovestone, Petroula Proitsi, Cristina Legido-Quigley, on behalf of the European Medical Information Framework Consortium
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
sex
Alzheimer’s disease
metabolomics
metabolic pathway
blood
vanillylmandelate
Biology (General)
QH301-705.5
Acceso en línea:https://doaj.org/article/6a6c1bacf1644613b95016a016cd9ea8
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Sumario: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, <i>APOE</i> ε4 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.

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