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.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Study ID	ST000047
Study Title	Identification of altered metabolic pathways in Alzheimer's disease, mild cognitive impairment and cognitively normals using Metabolomics (CSF)
Study Type	MS
Study Summary	Criteria 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
Department	Neurology
Last Name	Petersen
First Name	Ronald
Email	Dasari.Surendra@mayo.edu
Submit Date	2014-03-24
Num Groups	1
Total Subjects	15
Raw Data Available	Yes
Raw Data File Type(s)	d
Uploaded File Size	150 G
Analysis Type Detail	LC-MS
Release Date	2014-04-24
Release Version	1

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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
SA001981	Group1_11	AD
SA001982	Group1_10	AD
SA001983	Group1_12	AD
SA001984	Group1_13	AD
SA001985	Group1_1	AD
SA001986	Group1_14	AD
SA001987	Group1_9	AD
SA001988	Group1_15	AD
SA001989	Group1_3	AD
SA001990	Group1_2	AD
SA001991	Group1_8	AD
SA001992	Group1_4	AD
SA001993	Group1_5	AD
SA001994	Group1_7	AD
SA001995	Group1_6	AD
SA001996	Group3_36	CN
SA001997	Group3_38	CN
SA001998	Group3_37	CN
SA001999	Group3_32	CN
SA002000	Group3_33	CN
SA002001	Group3_34	CN
SA002002	Group3_35	CN
SA002003	Group3_42	CN
SA002004	Group3_45	CN
SA002005	Group3_31	CN
SA002006	Group3_44	CN
SA002007	Group3_43	CN
SA002008	Group3_40	CN
SA002009	Group3_41	CN
SA002010	Group3_39	CN
SA002011	Group2_23	MCI
SA002012	Group2_20	MCI
SA002013	Group2_21	MCI
SA002014	Group2_19	MCI
SA002015	Group2_18	MCI
SA002016	Group2_16	MCI
SA002017	Group2_17	MCI
SA002018	Group2_22	MCI
SA002019	Group2_24	MCI
SA002020	Group2_28	MCI
SA002021	Group2_29	MCI
SA002022	Group2_27	MCI
SA002023	Group2_26	MCI
SA002024	Group2_25	MCI
SA002025	Group2_30	MCI

Showing results 1 to 45 of 45

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

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.

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	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:	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:	Waters high-strength silica (150 x 2.1mm,1.8um)
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:	Waters ethylene-bridged hybrid (150 x 2.1mm,1.7um)
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