Imperial College London
Alternate

Dr Matthew R. Lewis

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Senior Research Officer
 
 
 
//

Contact

 

matthew.lewis

 
 
//

Location

 

660Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Whiley:2021:10.1186/s13195-020-00741-z,
author = {Whiley, L and Chappell, KE and D'Hondt, E and Lewis, MR and Jimenez, B and Snowden, SG and Soininen, H and Kloszewska, I and Mecocci, P and Tsolaki, M and Vellas, B and Swann, JR and Hye, A and Lovestone, S and Legido-Quigley, C and Holmes, E},
doi = {10.1186/s13195-020-00741-z},
journal = {Alzheimers Research & Therapy},
pages = {1--18},
title = {Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer's disease},
url = {http://dx.doi.org/10.1186/s13195-020-00741-z},
volume = {13},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundBoth serotonergic signalling disruption and systemic inflammation have been associated with the pathogenesis of Alzheimer’s disease (AD). The common denominator linking the two is the catabolism of the essential amino acid, tryptophan. Metabolism via tryptophan hydroxylase results in serotonin synthesis, whilst metabolism via indoleamine 2,3-dioxygenase (IDO) results in kynurenine and its downstream derivatives. IDO is reported to be activated in times of host systemic inflammation and therefore is thought to influence both pathways. To investigate metabolic alterations in AD, a large-scale metabolic phenotyping study was conducted on both urine and serum samples collected from a multi-centre clinical cohort, consisting of individuals clinically diagnosed with AD, mild cognitive impairment (MCI) and age-matched controls.MethodsMetabolic phenotyping was applied to both urine (n = 560) and serum (n = 354) from the European-wide AddNeuroMed/Dementia Case Register (DCR) biobank repositories. Metabolite data were subsequently interrogated for inter-group differences; influence of gender and age; comparisons between two subgroups of MCI - versus those who remained cognitively stable at follow-up visits (sMCI); and those who underwent further cognitive decline (cMCI); and the impact of selective serotonin reuptake inhibitor (SSRI) medication on metabolite concentrations.ResultsResults revealed significantly lower metabolite concentrations of tryptophan pathway metabolites in the AD group: serotonin (urine, serum), 5-hydroxyindoleacetic acid (urine), kynurenine (serum), kynurenic acid (urine), tryptophan (urine, serum), xanthurenic acid (urine, serum), and kynurenine/tryptophan ratio (urine). For each listed metabolite, a decreasing trend in concentrations was observed in-line with clinical diagnosis: control > MCI > AD. There were no significant differences in the two MCI subgroups whilst SSRI medication status influenced o
AU  - Whiley,L
AU  - Chappell,KE
AU  - D'Hondt,E
AU  - Lewis,MR
AU  - Jimenez,B
AU  - Snowden,SG
AU  - Soininen,H
AU  - Kloszewska,I
AU  - Mecocci,P
AU  - Tsolaki,M
AU  - Vellas,B
AU  - Swann,JR
AU  - Hye,A
AU  - Lovestone,S
AU  - Legido-Quigley,C
AU  - Holmes,E
DO  - 10.1186/s13195-020-00741-z
EP  - 18
PY  - 2021///
SN  - 1758-9193
SP  - 1
TI  - Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer's disease
T2  - Alzheimers Research & Therapy
UR  - http://dx.doi.org/10.1186/s13195-020-00741-z
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000606419700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://alzres.biomedcentral.com/articles/10.1186/s13195-020-00741-z
UR  - http://hdl.handle.net/10044/1/86609
VL  - 13
ER  -
Download