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.
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
UR - http://www.scopus.com/inward/record.url?scp=79956130559&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2010.06.001
DO - 10.1016/j.jalz.2010.06.001
M3 - 文章
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 -
