Summary of study ST000047

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 IDST000047
Study TitleIdentification of altered metabolic pathways in Alzheimer's disease, mild cognitive impairment and cognitively normals using Metabolomics (CSF)
Study TypeMS
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).bin,.xml,.stg,.m
Uploaded File Size150 G
Analysis Type DetailLC-MS
Release Date2014-04-24
Release Version1
Ronald Petersen Ronald Petersen
https://dx.doi.org/10.21228/M88G6G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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:SU000065
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
SA001981Group1_11AD
SA001982Group1_10AD
SA001983Group1_12AD
SA001984Group1_13AD
SA001985Group1_1AD
SA001986Group1_14AD
SA001987Group1_9AD
SA001988Group1_15AD
SA001989Group1_3AD
SA001990Group1_2AD
SA001991Group1_8AD
SA001992Group1_4AD
SA001993Group1_5AD
SA001994Group1_7AD
SA001995Group1_6AD
SA001996Group3_36CN
SA001997Group3_38CN
SA001998Group3_37CN
SA001999Group3_32CN
SA002000Group3_33CN
SA002001Group3_34CN
SA002002Group3_35CN
SA002003Group3_42CN
SA002004Group3_45CN
SA002005Group3_31CN
SA002006Group3_44CN
SA002007Group3_43CN
SA002008Group3_40CN
SA002009Group3_41CN
SA002010Group3_39CN
SA002011Group2_23MCI
SA002012Group2_20MCI
SA002013Group2_21MCI
SA002014Group2_19MCI
SA002015Group2_18MCI
SA002016Group2_16MCI
SA002017Group2_17MCI
SA002018Group2_22MCI
SA002019Group2_24MCI
SA002020Group2_28MCI
SA002021Group2_29MCI
SA002022Group2_27MCI
SA002023Group2_26MCI
SA002024Group2_25MCI
SA002025Group2_30MCI
Showing results 1 to 45 of 45

Collection:

Collection ID:CO000048
Collection Summary:CSF was collected from individuals in the fasting state by a lumbar puncture while lying on their side or in a seated position.
Sample Type:CSF
Collection Location:Lumbar puncture

Treatment:

Treatment ID:TR000066

Sample Preparation:

Sampleprep ID:SP000061
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 −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 −20°C prior to analysis. The samples were reconstituted in running buffer and analyzed within 24 hrs.

Combined analysis:

Analysis ID AN000080 AN000081 AN000082 AN000083
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 high-strength silica 2.1 150 mm, 1.8 m; Waters ethylene-bridged hybrid 2.1 150 mm, 1.7 m; Waters high-strength silica 2.1 150 mm, 1.8 m; Waters ethylene-bridged hybrid 2.1 150 mm, 1.7 m; Waters
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:CH000051
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:high-strength silica 2.1 150 mm, 1.8 m; Waters
Chromatography Type:Reversed phase
  
Chromatography ID:CH000052
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:ethylene-bridged hybrid 2.1 150 mm, 1.7 m; Waters
Chromatography Type:HILIC

MS:

MS ID:MS000061
Analysis ID:AN000080
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 (ESI) modes using a scan range of 50-1,200 m/z. The mass accuracy and mass resolution were 5 parts per million (ppm) and 20,000 ppm, 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:MS000062
Analysis ID:AN000081
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 (ESI) modes using a scan range of 50-1,200 m/z. The mass accuracy and mass resolution were 5 parts per million (ppm) and 20,000 ppm, 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:MS000063
Analysis ID:AN000082
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 (ESI) modes using a scan range of 50-1,200 m/z. The mass accuracy and mass resolution were 5 parts per million (ppm) and 20,000 ppm, 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:MS000064
Analysis ID:AN000083
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 (ESI) modes using a scan range of 50-1,200 m/z. The mass accuracy and mass resolution were 5 parts per million (ppm) and 20,000 ppm, 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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