Summary of Study ST000046

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000045. The data can be accessed directly via it's Project DOI: 10.21228/M88G6G This work is supported by NIH grant, U2C- DK119886.


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Study IDST000046
Study TitleIdentification of altered metabolic pathways in Alzheimer's disease, mild cognitive impairment and cognitively normals using Metabolomics (plasma)
Study SummaryCriteria for the diagnosis of amnestic MCI included: (i) memory complaint documented by the patient and collateral source; (ii) impairment in 1 or more of the 4 cognitive domains (memory, executive functioning/attention, visuospatial, or language); (iii) essentially normal functional activities of daily living; and (iv) absence of dementia. In general, the amnestic MCI determination is made when the memory measures fall 1.0–1.5 SD below the means for age and education appropriate individuals in our community; however, rigid cutoffs on psychometric scores were not used to establish the diagnosis of amnestic MCI which was made on clinical grounds. The diagnosis of dementia was made using DSM-IV criteria, and the diagnosis of AD was made using established criteria. Subjects were considered to be CN if they performed within the normative range and did not meet criteria for MCI or dementia.
Mayo Clinic
Last NamePetersen
First NameRonald
Submit Date2014-03-24
Num Groups1
Total Subjects15
Raw Data AvailableYes
Raw Data File Type(s)d
Uploaded File Size150 G
Analysis Type DetailLC-MS
Release Date2014-04-25
Release Version1
Ronald Petersen Ronald Petersen application/zip

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Project ID:PR000045
Project DOI:doi: 10.21228/M88G6G
Project Title:Identification of Altered Metabolic Pathways in Plasma and CSF in Mild Cognitive Impairment and Alzheimer’s Disease Using Metabolomics
Project Type:Untargeted LC-MS Metabolomics
Project Summary:Alzheimer’s Disease (AD) currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF) from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI) vs. cognitively normal (CN) individuals with a false discovery rate <0.05. The number of affected pathways increased with disease severity in both fluids. Lysine metabolism in plasma and the Krebs cycle in CSF were significantly affected in MCI vs. CN. Cholesterol and sphingolipids transport was altered in both CSF and plasma of AD vs. CN. Other 30 canonical pathways significantly disturbed in MCI and AD patients included energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis. Pathways in plasma that discriminated between all groups included polyamine, lysine, tryptophan metabolism, and aminoacyl-tRNA biosynthesis; and in CSF involved cortisone and prostaglandin 2 biosynthesis and metabolism. Our data suggest metabolomics could advance our understanding of the early disease mechanisms shared in progression from CN to MCI and to AD.
Institute:Mayo Clinic
Last Name:Petersen
First Name:Ronald
Address:200 First Street SW, Rochester, MN 55905
Funding Source:R01ES020715, AG006786, AG016574
Project Comments:Pubmed ID: 23700429