Summary of Study ST000046

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, 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.
Institute
Mayo Clinic
DepartmentNeurology
Last NamePetersen
First NameRonald
EmailDasari.Surendra@mayo.edu
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
https://dx.doi.org/10.21228/M88G6G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

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
Department:Neurology
Last Name:Petersen
First Name:Ronald
Address:200 First Street SW, Rochester, MN 55905
Email:Dasari.Surendra@mayo.edu
Phone:507-284-0513
Funding Source:R01ES020715, AG006786, AG016574
Project Comments:Pubmed ID: 23700429

Subject:

Subject ID:SU000064
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Human

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Cognitive Status
SA001936Group1_11AD
SA001937Group1_10AD
SA001938Group1_12AD
SA001939Group1_13AD
SA001940Group1_1AD
SA001941Group1_14AD
SA001942Group1_9AD
SA001943Group1_15AD
SA001944Group1_3AD
SA001945Group1_2AD
SA001946Group1_8AD
SA001947Group1_4AD
SA001948Group1_5AD
SA001949Group1_7AD
SA001950Group1_6AD
SA001951Group3_36CN
SA001952Group3_38CN
SA001953Group3_37CN
SA001954Group3_32CN
SA001955Group3_33CN
SA001956Group3_34CN
SA001957Group3_35CN
SA001958Group3_42CN
SA001959Group3_45CN
SA001960Group3_31CN
SA001961Group3_44CN
SA001962Group3_43CN
SA001963Group3_40CN
SA001964Group3_41CN
SA001965Group3_39CN
SA001966Group2_23MCI
SA001967Group2_20MCI
SA001968Group2_21MCI
SA001969Group2_19MCI
SA001970Group2_18MCI
SA001971Group2_16MCI
SA001972Group2_17MCI
SA001973Group2_22MCI
SA001974Group2_24MCI
SA001975Group2_28MCI
SA001976Group2_29MCI
SA001977Group2_27MCI
SA001978Group2_26MCI
SA001979Group2_25MCI
SA001980Group2_30MCI
Showing results 1 to 45 of 45

Collection:

Collection ID:CO000047
Collection Summary:Plasma was collected in EDTA tubes from individuals after an overnight fast using standard venipuncture procedures.
Sample Type:Plasma
Collection Location:standard venipuncture

Treatment:

Treatment ID:TR000065

Sample Preparation:

Sampleprep ID:SP000060
Sampleprep Summary:The metabolite extraction method was performed as described previously [PMID: 22415876] with minor modifications in the method. Plasma and CSF samples (100 µL) were thawed on ice at 4°C followed by deproteinization with methanol (1:4 ratio of plasma to methanol) and vortexed for 10 s, followed by incubation at â??20°C for 2 h. Prior to deproteinization, 4 µL of an internal standard solution of 13C6-Phenylalanine (247 ng/µL) was added to each plasma, CSF, and quality control (QC) samples to monitor the recovery of extracted metabolites. The samples were centrifuged at 18000 g for 20 min at 4°C. The supernatants were lyophilized (Savant, Holbrook, NY) and stored at â??20°C prior to analysis. The samples were reconstituted in running buffer and analyzed within 24 hrs.

Combined analysis:

Analysis ID AN000076 AN000077 AN000078 AN000079
Analysis type MS MS MS MS
Chromatography type Reversed phase HILIC Reversed phase HILIC
Chromatography system Waters Acquity Waters Acquity Waters Acquity Waters Acquity
Column Waters high-strength silica (150 x 2.1mm,1.8um) Waters ethylene-bridged hybrid (150 x 2.1mm,1.7um) Waters high-strength silica (150 x 2.1mm,1.8um) Waters ethylene-bridged hybrid (150 x 2.1mm,1.7um)
MS Type ESI ESI ESI ESI
MS instrument type TOF TOF TOF TOF
MS instrument name Agilent 6220 TOF Agilent 6220 TOF Agilent 6220 TOF Agilent 6220 TOF
Ion Mode POSITIVE POSITIVE NEGATIVE NEGATIVE
Units Raw MS Intensities Raw MS Intensities Raw MS Intensities Raw MS Intensities

Chromatography:

Chromatography ID:CH000049
Chromatography Summary:C18
Chromatography Comments:Metabolite separation in plasma and CSF was achieved using an Acquity UPLC system (Waters, Milford, MA) with both hydrophilic interaction chromatography (HILIC) (ethylene-bridged hybrid 2.1150 mm, 1.7 mm; Waters) and reversed-phase liquid chromatography C18 (RPLC) (high-strength silica 2.1150 mm, 1.8 m; Waters). For each column, the run time was 20 min at a flow rate of 400 L/min. Reverse-phase chromatography was performed using 99% solvent A (5 mmol/L NH4 acetate, 0.1% formic acid, and 1% acetonitrile) to 100% solvent B (95% acetonitrile with 0.1% formic acid). The gradient was 0 min, 0% B; 1 min, 0% B; 3 min, 5% B; 13.0 min, 100% B; 16 min, 100% B; 16.5 min, 0% B; and 20 min, 0% B. The hydrophilic interaction chromatography gradient was as follows: 0 min, 100% B; 1 min, 100% B; 5 min, 90% B; 13.0 min, 0% B; 16 min, 0% B; 16.5 min, 100% B; and 20 min, 100% B. The injection volume of each sample was 5 L and column was maintained at 50C. Each sample was injected and analyzed in duplicate.
Instrument Name:Waters Acquity
Column Name:Waters high-strength silica (150 x 2.1mm,1.8um)
Chromatography Type:Reversed phase
  
Chromatography ID:CH000050
Chromatography Summary:HILIC
Chromatography Comments:Metabolite separation in plasma and CSF was achieved using an Acquity UPLC system (Waters, Milford, MA) with both hydrophilic interaction chromatography (HILIC) (ethylene-bridged hybrid 2.1150 mm, 1.7 mm; Waters) and reversed-phase liquid chromatography C18 (RPLC) (high-strength silica 2.1150 mm, 1.8 m; Waters). For each column, the run time was 20 min at a flow rate of 400 L/min. Reverse-phase chromatography was performed using 99% solvent A (5 mmol/L NH4 acetate, 0.1% formic acid, and 1% acetonitrile) to 100% solvent B (95% acetonitrile with 0.1% formic acid). The gradient was 0 min, 0% B; 1 min, 0% B; 3 min, 5% B; 13.0 min, 100% B; 16 min, 100% B; 16.5 min, 0% B; and 20 min, 0% B. The hydrophilic interaction chromatography gradient was as follows: 0 min, 100% B; 1 min, 100% B; 5 min, 90% B; 13.0 min, 0% B; 16 min, 0% B; 16.5 min, 100% B; and 20 min, 100% B. The injection volume of each sample was 5 L and column was maintained at 50C. Each sample was injected and analyzed in duplicate.
Instrument Name:Waters Acquity
Column Name:Waters ethylene-bridged hybrid (150 x 2.1mm,1.7um)
Chromatography Type:HILIC

MS:

MS ID:MS000057
Analysis ID:AN000076
Instrument Name:Agilent 6220 TOF
Instrument Type:TOF
MS Type:ESI
MS Comments:Positive-ion mode/C18: A 6220 ToF MS (Agilent Technologies) was operated in both positive and negative electrospray ionization modes using a scan range of 50â??1,200 m/z. The mass accuracy and mass resolution were <5 parts per million (ppm) and â?¼20,000, respectively. The instrument settings were as follows: nebulizer gas temperature 325°C, capillary voltage 3.5 kV, capillary temperature 300°C, fragmentor voltage 150 V, skimmer voltage 58 V, octapole voltage 250 V, cycle time 0.5 s, and run time 15.0 min.
Ion Mode:POSITIVE
  
MS ID:MS000058
Analysis ID:AN000077
Instrument Name:Agilent 6220 TOF
Instrument Type:TOF
MS Type:ESI
MS Comments:Positive-ion mode/HILIC: A 6220 ToF MS (Agilent Technologies) was operated in both positive and negative electrospray ionization modes using a scan range of 50â??1,200 m/z. The mass accuracy and mass resolution were <5 parts per million (ppm) and â?¼20,000, respectively. The instrument settings were as follows: nebulizer gas temperature 325°C, capillary voltage 3.5 kV, capillary temperature 300°C, fragmentor voltage 150 V, skimmer voltage 58 V, octapole voltage 250 V, cycle time 0.5 s, and run time 15.0 min.
Ion Mode:POSITIVE
  
MS ID:MS000059
Analysis ID:AN000078
Instrument Name:Agilent 6220 TOF
Instrument Type:TOF
MS Type:ESI
MS Comments:Negative-ion mode/C18: A 6220 ToF MS (Agilent Technologies) was operated in both positive and negative electrospray ionization modes using a scan range of 50â??1,200 m/z. The mass accuracy and mass resolution were <5 parts per million (ppm) and â?¼20,000, respectively. The instrument settings were as follows: nebulizer gas temperature 325°C, capillary voltage 3.5 kV, capillary temperature 300°C, fragmentor voltage 150 V, skimmer voltage 58 V, octapole voltage 250 V, cycle time 0.5 s, and run time 15.0 min.
Ion Mode:NEGATIVE
  
MS ID:MS000060
Analysis ID:AN000079
Instrument Name:Agilent 6220 TOF
Instrument Type:TOF
MS Type:ESI
MS Comments:Negative-ion mode/HILIC: A 6220 ToF MS (Agilent Technologies) was operated in both positive and negative electrospray ionization modes using a scan range of 50â??1,200 m/z. The mass accuracy and mass resolution were <5 parts per million (ppm) and â?¼20,000, respectively. The instrument settings were as follows: nebulizer gas temperature 325°C, capillary voltage 3.5 kV, capillary temperature 300°C, fragmentor voltage 150 V, skimmer voltage 58 V, octapole voltage 250 V, cycle time 0.5 s, and run time 15.0 min.
Ion Mode:NEGATIVE
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