Sex-Specific Metabolic Pathways Were Associated with Alzheimer's Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort.
Alzheimer’s disease
blood
metabolic pathway
metabolomics
sex
tryptophan betaine
vanillylmandelate
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
03 Nov 2021
03 Nov 2021
Historique:
received:
04
10
2021
revised:
22
10
2021
accepted:
25
10
2021
entrez:
27
11
2021
pubmed:
28
11
2021
medline:
28
11
2021
Statut:
epublish
Résumé
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. 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, 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). 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.
Sections du résumé
BACKGROUND
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
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,
RESULTS
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
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.
Identifiants
pubmed: 34829839
pii: biomedicines9111610
doi: 10.3390/biomedicines9111610
pmc: PMC8615383
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Stat Med. 2017 Dec 10;36(28):4455-4467
pubmed: 27426413
Neuroscience. 2007 Aug 10;148(1):188-97
pubmed: 17629627
J Intern Med. 2004 Sep;256(3):183-94
pubmed: 15324362
Alzheimers Dement. 2019 Jun;15(6):817-827
pubmed: 31078433
Alzheimers Res Ther. 2017 Feb 2;9(1):6
pubmed: 28153054
Neurosci Biobehav Rev. 2014 Feb;39:34-50
pubmed: 24374381
Adv Med Sci. 2010;55(2):204-11
pubmed: 20639188
J Alzheimers Dis. 2017;60(2):495-504
pubmed: 28869479
Neurology. 2016 Aug 2;87(5):539-47
pubmed: 27371494
Psychiatr Times. 2018 Nov;35(11):14-17
pubmed: 30820070
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Nat Rev Neurol. 2018 Aug;14(8):457-469
pubmed: 29985474
Microbiome. 2019 Jul 10;7(1):103
pubmed: 31291994
JAMA. 2020 Aug 25;324(8):772-781
pubmed: 32722745
BMC Neurosci. 2009 Sep 30;10:125
pubmed: 19793392
Stat Med. 2008 Jan 30;27(2):157-72; discussion 207-12
pubmed: 17569110
Alzheimers Res Ther. 2012 Feb 01;4(1):5
pubmed: 22293144
Eur Heart J. 2019 Jun 14;40(23):1880-1887
pubmed: 29955849
PLoS One. 2016 May 19;11(5):e0155694
pubmed: 27196316
BMC Complement Altern Med. 2017 Feb 20;17(1):120
pubmed: 28219355
Lancet. 2021 Apr 24;397(10284):1577-1590
pubmed: 33667416
Clin Biochem. 2010 Aug;43(12):992-7
pubmed: 20457143
J Neurosci Res. 2017 Jan 2;95(1-2):671-680
pubmed: 27870425
Alzheimers Dement (N Y). 2019 Oct 14;5:597-609
pubmed: 31650016
J Alzheimers Dis. 2017;60(3):1025-1034
pubmed: 28984603
Eur J Nucl Med Mol Imaging. 2016 Jan;43(1):142-151
pubmed: 26260650
J Cereb Blood Flow Metab. 2016 Jan;36(1):95-113
pubmed: 26219595
Transl Psychiatry. 2013 Apr 09;3:e244
pubmed: 23571809
J Neurol Neurosurg Psychiatry. 2015 Dec;86(12):1299-306
pubmed: 26294005
JAMA Netw Open. 2021 Mar 1;4(3):e211001
pubmed: 33687445
Neurochem Int. 2011 Jan;58(1):60-8
pubmed: 21075154
J Alzheimers Dis. 2010;22(3):909-22
pubmed: 20858974
J Alzheimers Dis. 2016 Aug 10;54(1):383-95
pubmed: 27567807
Transl Psychiatry. 2019 Jan 17;9(1):19
pubmed: 30655505
Neurology. 1984 Jul;34(7):939-44
pubmed: 6610841
J Alzheimers Dis. 2012;31(4):717-24
pubmed: 22710913
Inflamm Res. 2018 Jan;67(1):67-75
pubmed: 28956064
Alzheimers Dement (N Y). 2019 Dec 18;5:933-938
pubmed: 31890857
Alzheimers Res Ther. 2019 Nov 28;11(1):93
pubmed: 31779690
Annu Rev Pathol. 2015;10:291-319
pubmed: 25387055
Neurochem Int. 2007 Jan;50(2):308-13
pubmed: 17023091
J Alzheimers Dis. 2014;41(1):313-27
pubmed: 24614907
J Intern Med. 2016 Jun;279(6):576-91
pubmed: 26940242
Alzheimers Res Ther. 2018 Jul 6;10(1):64
pubmed: 29980228
Neurobiol Aging. 2017 Feb;50:144-151
pubmed: 27916386
Lancet Neurol. 2020 May;19(5):422-433
pubmed: 32333900
Neuroepidemiology. 2008;30(4):254-65
pubmed: 18515975