Sex-specific metabolic pathways were associated with alzheimer's disease (Ad) endophenotypes in the european medical information framework for ad multimodal biomarker discovery cohort
Xu, Jin (King's College London)
Green, Becki (King's College London)
Kim, Min (Steno Diabetes Center)
Lord, Jodie (King's College London)
Ebshiana, Amera (King's College London)
Westwood, Sarah (University of Oxford. Department of Psychiatry)
Baird, Alison (University of Oxford. Department of Psychiatry)
Nevado-Holgado, Alejo (University of Oxford. Department of Psychiatry)
Shi, Liu (University of Oxford. Department of Psychiatry)
Hye, Abdul (King's College London)
Snowden, Stuart (King's College London)
Bos, Isabelle (Maastricht University (Països Baixos))
Vos, Stephanie J. B. (Maastricht University (Països Baixos))
Vandenberghe, Rik (VU University Medical Center. Alzheimer Center (Països Baixos))
Teunissen, Charlotte E. (VU University Medical Center. Department of Radiology and Nuclear Medicine (Països Baixos))
Kate, Mara Ten (VU University Medical Center. Department of Radiology and Nuclear Medicine (Països Baixos))
Scheltens, Philip (VU University Medical Center (Països Baixos))
Gabel, Silvy (University Hospitals Leuven (Bèlgica))
Meersmans, Karen (University Hospitals Leuven (Bèlgica))
Blin, Olivier (Aix-Marseille Université (França))
Richardson, Jill (GlaxoSmithKline R&D (Regne Unit))
De Roeck, Ellen E. (University of Antwerp (Països Baixos))
Engelborghs, Sebastiaan (University of Antwerp (Països Baixos))
Sleegers, Kristel (Complex Genetics of Alzheimer's Disease Group. VIB Center for Molecular Neurology. VIB)
Bordet, Régis (Université de Lille. Department of Medical Pharmacology)
Rami Gonzalez, Lorena (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Kettunen, Petronella (University of Gothenburg)
Tsolaki, Magda (AHEPA University Hospital (Grècia))
Verhey, Frans R. J. (Maastricht University. Alzheimer Centrum Limburg (Països Baixos))
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Peyratout, Gwendoline (Lausanne University Hospital)
Tainta, Mikel (Fundación CITA-Alzhéimer Fundazioa)
Johannsen, Peter (Danish Dementia Research Centre. Rigshospitalet)
Freund-Levi, Yvonne (King's College London)
Froelich, Lutz (University of Heidelberg. Department of Geriatric Psychiatry (Alemanya))
Dobricic, Valerija (University of Lübeck. Institutes of Neurogenetics and Cardiogenetics)
Frisoni, Giovanni B. (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Molinuevo, José Luis (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Wallin, Anders (Sahlgrenska Academy at University of Gothenburg (Suècia))
Popp, Julius (University Hospital of Psychiatry Zürich (Suïssa))
Martinez-Lage, Pablo (Fundación CITA-Alzhéimer Fundazioa (San Sebastián, País Basc))
Bertram, Lars (University of Oslo. Department of Psychology)
Blennow, Kaj (Sahlgrenska University Hospital (Suècia))
Zetterberg, Henrik (UCL Institute of Neurology (Regne Unit))
Streffer, Johannes (University of Antwerp (Països Baixos))
Visser, Pieter Jelle (Maastricht University. Alzheimer Centrum Limburg (Països Baixos))
Lovestone, Simon (King's College London)
Proitsi, Petroula (King's College London)
Legido-Quigley, Cristina (King's College London. Institute of Pharmaceutical Science)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	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, APOE 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.
Ayudas:	European Commission. Horizon 2020 666992 European Commission QLRT-2001-2455 European Commission 37670 European Commission 681712 European Commission. Horizon 2020 860197 European Commission JPND2019-466-236 Instituto de Salud Carlos III PI18-00435 Instituto de Salud Carlos III INT19-00016 Agència de Gestió d'Ajuts Universitaris i de Recerca SLT006-17-125
Nota:	Altres ajuts: Fundació Bancària Obra Social La Caixa, Fundació Catalana Síndrome de Down, Fundació La Marató de TV3, Fundación Española para el Fomento de la Investigación de la Esclerosis Lateral Amiotrófica, Fundación BBVA i Fundació Víctor Grífols i Lucas
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Sex ; Alzheimer's disease ; Metabolomics ; Metabolic pathway ; Blood ; Vanillylmandelate ; Tryptophan betaine
Publicado en:	Biomedicines, Vol. 9 Núm. 11 (november 2021) , p. 1610, ISSN 2227-9059

DOI: 10.3390/biomedicines9111610
PMID: 34829839

15 p, 2.1 MB

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