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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2021
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oai:doaj.org-article:6a6c1bacf1644613b95016a016cd9ea82021-11-25T16:49:36ZSex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort10.3390/biomedicines91116102227-9059https://doaj.org/article/6a6c1bacf1644613b95016a016cd9ea82021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1610https://doaj.org/toc/2227-9059Background: 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.Jin XuRebecca GreenMin KimJodie LordAmera EbshianaSarah WestwoodAlison L. BairdAlejo J. Nevado-HolgadoLiu ShiAbdul HyeStuart G. SnowdenIsabelle BosStephanie J. B. VosRik VandenbergheCharlotte E. TeunissenMara Ten KatePhilip ScheltensSilvy GabelKaren MeersmansOlivier BlinJill RichardsonEllen Elisa De RoeckSebastiaan EngelborghsKristel SleegersRégis BordetLorena RamiPetronella KettunenMagda TsolakiFrans R. J. VerheyDaniel AlcoleaAlberto LleóGwendoline PeyratoutMikel TaintaPeter JohannsenYvonne Freund-LeviLutz FrölichValerija DobricicGiovanni B. FrisoniJosé Luis MolinuevoAnders WallinJulius PoppPablo Martinez-LageLars BertramKaj BlennowHenrik ZetterbergJohannes StrefferPieter Jelle VisserSimon LovestonePetroula ProitsiCristina Legido-Quigleyon behalf of the European Medical Information Framework ConsortiumMDPI AGarticlesexAlzheimer’s diseasemetabolomicsmetabolic pathwaybloodvanillylmandelateBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1610, p 1610 (2021) |
| institution |
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| collection |
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| language |
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| topic |
sex Alzheimer’s disease metabolomics metabolic pathway blood vanillylmandelate Biology (General) QH301-705.5 |
| spellingShingle |
sex Alzheimer’s disease metabolomics metabolic pathway blood vanillylmandelate Biology (General) QH301-705.5 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 Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Jin Xu |
| title |
Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort |
| title_short |
Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort |
| title_full |
Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort |
| title_fullStr |
Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort |
| title_full_unstemmed |
Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort |
| title_sort |
sex-specific metabolic pathways were associated with alzheimer’s disease (ad) endophenotypes in the european medical information framework for ad multimodal biomarker discovery cohort |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/6a6c1bacf1644613b95016a016cd9ea8 |
| work_keys_str_mv |
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