Please use this identifier to cite or link to this item: https://doi.org/10.1038/tp.2013.18
Title: Alterations in metabolic pathways and networks in Alzheimer's disease
Authors: Kaddurah-Daouk, R.
Zhu, H.
Sharma, S.
Bogdanov, M.
Rozen, S.G. 
Matson, W.
Oki, N.O.
Motsinger-Reif, A.A.
Churchill, E.
Lei, Z.
Appleby, D.
Kling, M.A.
Trojanowski, J.Q.
Doraiswamy, P.M.
Arnold, S.E.
Keywords: Alzheimer's disease
Metabolomics
Partial network reconstruction
Pathway analysis
Issue Date: 2013
Citation: Kaddurah-Daouk, R., Zhu, H., Sharma, S., Bogdanov, M., Rozen, S.G., Matson, W., Oki, N.O., Motsinger-Reif, A.A., Churchill, E., Lei, Z., Appleby, D., Kling, M.A., Trojanowski, J.Q., Doraiswamy, P.M., Arnold, S.E. (2013). Alterations in metabolic pathways and networks in Alzheimer's disease. Translational Psychiatry 3 : -. ScholarBank@NUS Repository. https://doi.org/10.1038/tp.2013.18
Abstract: The pathogenic mechanisms of Alzheimer's disease (AD) remain largely unknown and clinical trials have not demonstrated significant benefit. Biochemical characterization of AD and its prodromal phase may provide new diagnostic and therapeutic insights. We used targeted metabolomics platform to profile cerebrospinal fluid (CSF) from AD (n=40), mild cognitive impairment (MCI, n=36) and control (n=38) subjects; univariate and multivariate analyses to define between-group differences; and partial least square-discriminant analysis models to classify diagnostic groups using CSF metabolomic profiles. A partial correlation network was built to link metabolic markers, protein markers and disease severity. AD subjects had elevated methionine (MET), 5-hydroxyindoleacetic acid (5-HIAA), vanillylmandelic acid, xanthosine and glutathione versus controls. MCI subjects had elevated 5-HIAA, MET, hypoxanthine and other metabolites versus controls. Metabolite ratios revealed changes within tryptophan, MET and purine pathways. Initial pathway analyses identified steps in several pathways that appear altered in AD and MCI. A partial correlation network showed total tau most directly related to norepinephrine and purine pathways; amyloid-β (Ab42) was related directly to an unidentified metabolite and indirectly to 5-HIAA and MET. These findings indicate that MCI and AD are associated with an overlapping pattern of perturbations in tryptophan, tyrosine, MET and purine pathways, and suggest that profound biochemical alterations are linked to abnormal Ab42 and tau metabolism. Metabolomics provides powerful tools to map interlinked biochemical pathway perturbations and study AD as a disease of network failure. © 2013 Macmillan Publishers Limited.
Source Title: Translational Psychiatry
URI: http://scholarbank.nus.edu.sg/handle/10635/109918
ISSN: 21583188
DOI: 10.1038/tp.2013.18
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

61
checked on May 26, 2018

WEB OF SCIENCETM
Citations

57
checked on Apr 3, 2018

Page view(s)

50
checked on May 25, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.