Summary of Study ST002442

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 PR001573. The data can be accessed directly via it's Project DOI: 10.21228/M8CD9V This work is supported by NIH grant, U2C- DK119886.

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

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study ID	ST002442
Study Title	Alterations in CSF Urea Occur in Late Manifest Stage Huntington Disease
Study Type	untargeted metabolomics analysis
Study Summary	Huntington Disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and post-mortem tissues of HD patients. The exact timing of these elevations in urea and the molecular mechanism(s) responsible for these disturbances remain unknown. To better understand the pathophysiologic mechanisms responsible for elevations in urea in HD, we completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late-manifest (LATE) HD participants compared to controls. We found approximately 500 metabolites were significantly altered in pre-manifest participants compared to controls, although no significant difference in CSF urea or urea metabolites. Interestingly, CSF urea was only significantly elevated in LATE participants compared to controls. There were no changes in the urea metabolites, citrulline, ornithine and arginine throughout disease; however, we did observe changes in acetate, creatinine, 4-acetamidobutanoate and 4-aminobutyraldehyde which are indirect modifiers of urea. Overall, our study confirms that elevations in urea do occur in HD, albeit later in disease and that these changes may reflect more central impairments to cellular energy metabolism yet to be explored.
Institute	Vanderbilt University
Department	Chemistry
Laboratory	Center for Innovative Technology
Last Name	CODREANU
First Name	SIMONA
Address	1234 STEVENSON CENTER LANE
Email	SIMONA.CODREANU@VANDERBILT.EDU
Phone	6158758422
Submit Date	2023-01-12
Num Groups	4
Total Subjects	60
Raw Data Available	Yes
Raw Data File Type(s)	raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2023-01-25
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP002537
Sampleprep Summary:	CSF samples collected were flash frozen and stored at -80°C until analyzed via Liquid ChromatographyHigh Resolution Mass Spectrometry (LC-HRMS and LC-HRMS/MS)-based metabolomics in the Vanderbilt Center for Innovative Technology (CIT) using previously described methods (cite). Briefly, equal volumes (100 µL) of previously frozen CSF was diluted with 100 µL ice-cold lysis buffer (1:1:2, Acetonitrile:MeOH:Ammonium Bicarbonate 0.1M, pH 8.0, LC-MS grade). Addition of isotopically labeled phenylalanine-D8 and biotin-D2 were added to individual samples prior to protein precipitation by addition of 800 µL of ice-cold methanol. Following overnight incubation at -80°C, precipitated proteins were pelleted by centrifugation at 10,000 rpm for 10 min and metabolite extracts were dried down in vacuo and stored at -80°C until reconstitution prior to MS analysis.

Sampleprep ID:

SP002537

Sampleprep Summary:

CSF samples collected were flash frozen and stored at -80°C until analyzed via Liquid ChromatographyHigh Resolution Mass Spectrometry (LC-HRMS and LC-HRMS/MS)-based metabolomics in the Vanderbilt Center for Innovative Technology (CIT) using previously described methods (cite). Briefly, equal volumes (100 µL) of previously frozen CSF was diluted with 100 µL ice-cold lysis buffer (1:1:2, Acetonitrile:MeOH:Ammonium Bicarbonate 0.1M, pH 8.0, LC-MS grade). Addition of isotopically labeled phenylalanine-D8 and biotin-D2 were added to individual samples prior to protein precipitation by addition of 800 µL of ice-cold methanol. Following overnight incubation at -80°C, precipitated proteins were pelleted by centrifugation at 10,000 rpm for 10 min and metabolite extracts were dried down in vacuo and stored at -80°C until reconstitution prior to MS analysis.