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, J. (King's College London)
Green, R. (King's College London)
Kim, M. (Steno Diabetes Center)
Lord, J. (King's College London)
Ebshiana, A. (King's College London)
Westwood, S. (Department of Psychiatry. University of Oxford)
Baird, Alison L (Department of Psychiatry. University of Oxford)
Nevado-Holgado, Alejo (Department of Psychiatry. University of Oxford)
Shi, L. (Department of Psychiatry. University of Oxford)
Hye, Abdul (King's College London)
Snowden, S. G. (King's College London)
Bos, Isabelle (Amsterdam UMC. University Medical Center)
Vos, S. J. B. (Maastricht University)
Vandenberghe, Rik (Alzheimer Center. VU University Medical Center)
Teunissen, C. E. (Department of Radiology and Nuclear Medicine. VU University Medical Center)
Kate, M. T. (Department of Radiology and Nuclear Medicine. VU University Medical Center)
Scheltens, P. (Alzheimer Center. VU University Medical Center)
Gabel, Silvy (University Hospitals Leuven (Bèlgica))
Meersmans, K. (University Hospitals Leuven (Bèlgica))
Blin, Olivier (Clinical Pharmacology & Pharmacovigilance Department. Aix-Marseille University-CNRS)
Richardson, J. (Neurosciences Therapeutic Area. GlaxoSmithKline R&D)
De Roeck, Ellen E (University of Antwerp. Institute Born-Bunge)
Engelborghs, Sebastiaan (RUniversity of Antwerp. Institute Born-Bunge)
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, F. R. J. (Maastricht University. Alzheimer Centrum Limburg)
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)
Frölich, L. (University of Heidelberg. Department of Geriatric Psychiatry)
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 (University of Gothenburg. Sahlgrenska Academy)
Popp, J. (University Hospital of Psychiatry Zürich)
Martinez-Lage, P. (Center for Research and Advanced Therapies. CITA-Alzheimer Foundation)
Bertram, Lars (University of Oslo. Department of Psychology)
Blennow, Kaj (Sahlgrenska University Hospital (Suècia))
Zetterberg, Henrik (UCL Institute of Neurology (Regne Unit))
Streffer, J. (Reference Center for Biological Markers of Dementia (BIODEM). Institute Born-Bunge. University of Antwerp)
Jelle Visser, P. (Maastricht University. Alzheimer Centrum Limburg)
Lovestone, Simon (Janssen-Cilag UK Ltd.)
Proitsi, P. (King's College London)
Legido-Quigley, Cristina (Steno Diabetes Center)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	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.
Ajuts:	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
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Sex ; Alzheimer's disease ; Metabolomics ; Metabolic pathway ; Blood ; Vanillylmandelate ; Tryptophan betaine
Publicat a:	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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