TY - JOUR
T1 - Metabolomic changes in autopsy-confirmed Alzheimer's disease
AU - Kaddurah-Daouk, Rima
AU - Rozen, Steve
AU - Matson, Wayne
AU - Han, Xianlin
AU - Hulette, Christine M.
AU - Burke, James R.
AU - Doraiswamy, P. Murali
AU - Welsh-Bohmer, Kathleen A.
N1 - Funding Information:
This research was supported in part with a grant from NIH ( R24 GM078233 ), “ The Metabolomics Research Network ” ( R01 NS054008-01A2 ) (R.K.-D.), and the Bryan ADRC ( P50 AG01528 and P30 AG028377 ). R.K.-D. has patents in this field, stock in Metabolon, and has received funding from pharmaceutical companies for metabolomic studies. K.W.B. has received in the past a research gift/grant from GSK through the Bryan ADRC. She has also served as a paid advisor to several pharmaceutical companies including GSK, Metabolon, and Pfizer. J.R.B. has been advisor to GSK. P.M.D. has received research grants (through Duke) and served as a paid advisor to several companies. He owns stock in Sonexa. X.H. serves as a consultant for the LipoSpectrum LLC.
PY - 2011/5
Y1 - 2011/5
N2 - Background: Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of several metabolites to identify metabolic perturbances that might provide insights into disease. Methods: In this pilot study, we took a targeted electrochemistry-based metabolomics approach where liquid chromatography followed by coulometric array detection enables quantification of over 30 metabolites within key neurotransmitter pathways (dopamine and serotonin) and pathways involved in oxidative stress. Results: Using samples from postmortem ventricular cerebrospinal fluid (15 Alzheimer's disease [AD] and 15 nondemented subjects with autopsy-confirmed diagnoses) and by using regression models, correlations, Wilcoxon rank-sum tests, and t-tests we identified alterations in tyrosine, tryptophan, purine, and tocopherol pathways in patients with AD. Reductions in norepinephrine and its related metabolites were also seen, consistent with previously published data. Conclusions: These data support further investigation of metabolomics in larger samples of clinical AD as well as in those with preclinical disease for use as biomarkers.
AB - Background: Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of several metabolites to identify metabolic perturbances that might provide insights into disease. Methods: In this pilot study, we took a targeted electrochemistry-based metabolomics approach where liquid chromatography followed by coulometric array detection enables quantification of over 30 metabolites within key neurotransmitter pathways (dopamine and serotonin) and pathways involved in oxidative stress. Results: Using samples from postmortem ventricular cerebrospinal fluid (15 Alzheimer's disease [AD] and 15 nondemented subjects with autopsy-confirmed diagnoses) and by using regression models, correlations, Wilcoxon rank-sum tests, and t-tests we identified alterations in tyrosine, tryptophan, purine, and tocopherol pathways in patients with AD. Reductions in norepinephrine and its related metabolites were also seen, consistent with previously published data. Conclusions: These data support further investigation of metabolomics in larger samples of clinical AD as well as in those with preclinical disease for use as biomarkers.
KW - Alzheimer's
KW - Biomarkers
KW - Diagnosis
KW - Metabolomics
KW - Purine
KW - Staging
KW - Tryptophan
KW - Tyrosine
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U2 - 10.1016/j.jalz.2010.06.001
DO - 10.1016/j.jalz.2010.06.001
M3 - Article
C2 - 21075060
AN - SCOPUS:79956130559
SN - 1552-5260
VL - 7
SP - 309
EP - 317
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 3
ER -