F10 Quantifying putative biomarkers of Huntington disease in blood and urine by selected reaction monitoring mass spectrometry
BackgroundAlthough the gene expansion associated with Huntington Disease (HD) is well known, the downstream effects are complex and poorly understood. Delineating molecular pathways that become disrupted in the presence of an expanded repeat protein will provide insight into the relationship between...
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description | BackgroundAlthough the gene expansion associated with Huntington Disease (HD) is well known, the downstream effects are complex and poorly understood. Delineating molecular pathways that become disrupted in the presence of an expanded repeat protein will provide insight into the relationship between the expression of proteins and underlying pathophysiology, and begin to point the way to tailored therapeutics.AimsProtein biomarkers can be sourced from bodily fluids, including blood plasma and urine, and may identify presence of disease, either before or after the appearance of signs or symptoms. The aim of the present study was to systematically profile protein expression in HD-expanded individuals, and relate these findings to metrics of disease severity.MethodsWe applied selected reaction monitoring (SRM) mass spectrometry (MS) proteomic profiling techniques to analyse samples from HD gene-expansion individuals that participated in PREDICT-HD. Plasma and urine samples, along with corresponding UHDRS Motor subscale scores, were supplied from 10 male HD motor manifest gene-expansion carriers (CAG repeat length >36; UHDRS Diagnostic Confidence Level >3) and 10 age-matched male controls (non-gene-expanded family members). Samples were collected as part of the PREDICT-HD protocol.ResultsCandidate proteins were identified to be differentially expressed in HD gene-expansion carriers relative to non-expanded familial controls. Moreover, within gene-expansion carriers, a sub-set of proteins were identified that were correlated with severity of motor manifestations, and may represent potential biomarkers of disease severity. Preliminary investigations using pooled specimens from these same patients revealed that some proteins showing differential expression in plasma appear to show similar differences in urine.ConclusionsUsing proteomic profiling techniques we have identified proteins showing differential expression in relation to HD, many of which to our knowledge have never before been measured in plasma. The identification of biomarkers through the use of SRM-MS holds great promise to increasing our understanding of HD. |
doi_str_mv | 10.1136/jnnp-2012-303524.75 |
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Delineating molecular pathways that become disrupted in the presence of an expanded repeat protein will provide insight into the relationship between the expression of proteins and underlying pathophysiology, and begin to point the way to tailored therapeutics.AimsProtein biomarkers can be sourced from bodily fluids, including blood plasma and urine, and may identify presence of disease, either before or after the appearance of signs or symptoms. The aim of the present study was to systematically profile protein expression in HD-expanded individuals, and relate these findings to metrics of disease severity.MethodsWe applied selected reaction monitoring (SRM) mass spectrometry (MS) proteomic profiling techniques to analyse samples from HD gene-expansion individuals that participated in PREDICT-HD. Plasma and urine samples, along with corresponding UHDRS Motor subscale scores, were supplied from 10 male HD motor manifest gene-expansion carriers (CAG repeat length >36; UHDRS Diagnostic Confidence Level >3) and 10 age-matched male controls (non-gene-expanded family members). Samples were collected as part of the PREDICT-HD protocol.ResultsCandidate proteins were identified to be differentially expressed in HD gene-expansion carriers relative to non-expanded familial controls. Moreover, within gene-expansion carriers, a sub-set of proteins were identified that were correlated with severity of motor manifestations, and may represent potential biomarkers of disease severity. Preliminary investigations using pooled specimens from these same patients revealed that some proteins showing differential expression in plasma appear to show similar differences in urine.ConclusionsUsing proteomic profiling techniques we have identified proteins showing differential expression in relation to HD, many of which to our knowledge have never before been measured in plasma. The identification of biomarkers through the use of SRM-MS holds great promise to increasing our understanding of HD.</description><identifier>ISSN: 0022-3050</identifier><identifier>EISSN: 1468-330X</identifier><identifier>DOI: 10.1136/jnnp-2012-303524.75</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd</publisher><subject>Biomarkers ; Huntingtons disease ; Mass spectrometry ; mass spectrometry (MS) ; protein biomarkers ; Proteins ; Proteomics ; Scientific imaging ; selected reaction monitoring (SRM) ; Urine</subject><ispartof>Journal of neurology, neurosurgery and psychiatry, 2012-09, Vol.83 (Suppl 1), p.A24-A24</ispartof><rights>2012, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><rights>2012 2012, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jnnp.bmj.com/content/83/Suppl_1/A24.1.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttps://jnnp.bmj.com/content/83/Suppl_1/A24.1.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,780,784,3196,23571,27924,27925,77600,77631</link.rule.ids></links><search><creatorcontrib>Evans, K</creatorcontrib><creatorcontrib>Ackloo, S</creatorcontrib><creatorcontrib>Chen, J</creatorcontrib><creatorcontrib>Dharsee, M</creatorcontrib><creatorcontrib>Li, J</creatorcontrib><creatorcontrib>Paulsen, J S</creatorcontrib><creatorcontrib>Sills, T</creatorcontrib><creatorcontrib>Vaccarino, A</creatorcontrib><creatorcontrib>and the and PREDICT-HD Investigators and Coordinators</creatorcontrib><title>F10 Quantifying putative biomarkers of Huntington disease in blood and urine by selected reaction monitoring mass spectrometry</title><title>Journal of neurology, neurosurgery and psychiatry</title><addtitle>J Neurol Neurosurg Psychiatry</addtitle><description>BackgroundAlthough the gene expansion associated with Huntington Disease (HD) is well known, the downstream effects are complex and poorly understood. Delineating molecular pathways that become disrupted in the presence of an expanded repeat protein will provide insight into the relationship between the expression of proteins and underlying pathophysiology, and begin to point the way to tailored therapeutics.AimsProtein biomarkers can be sourced from bodily fluids, including blood plasma and urine, and may identify presence of disease, either before or after the appearance of signs or symptoms. The aim of the present study was to systematically profile protein expression in HD-expanded individuals, and relate these findings to metrics of disease severity.MethodsWe applied selected reaction monitoring (SRM) mass spectrometry (MS) proteomic profiling techniques to analyse samples from HD gene-expansion individuals that participated in PREDICT-HD. Plasma and urine samples, along with corresponding UHDRS Motor subscale scores, were supplied from 10 male HD motor manifest gene-expansion carriers (CAG repeat length >36; UHDRS Diagnostic Confidence Level >3) and 10 age-matched male controls (non-gene-expanded family members). Samples were collected as part of the PREDICT-HD protocol.ResultsCandidate proteins were identified to be differentially expressed in HD gene-expansion carriers relative to non-expanded familial controls. Moreover, within gene-expansion carriers, a sub-set of proteins were identified that were correlated with severity of motor manifestations, and may represent potential biomarkers of disease severity. Preliminary investigations using pooled specimens from these same patients revealed that some proteins showing differential expression in plasma appear to show similar differences in urine.ConclusionsUsing proteomic profiling techniques we have identified proteins showing differential expression in relation to HD, many of which to our knowledge have never before been measured in plasma. The identification of biomarkers through the use of SRM-MS holds great promise to increasing our understanding of HD.</description><subject>Biomarkers</subject><subject>Huntingtons disease</subject><subject>Mass spectrometry</subject><subject>mass spectrometry (MS)</subject><subject>protein biomarkers</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Scientific imaging</subject><subject>selected reaction monitoring (SRM)</subject><subject>Urine</subject><issn>0022-3050</issn><issn>1468-330X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkMtq3DAUhkVJoZO0T9CNoGtPdLEka1mG3CC0hF53QpaloOlYciQ5dHbZ9EX7JJVxyTpncxbn-_8DHwDvMdpiTPn5PoSpIQiThiLKSLsV7BXY4JZ3DaXo5wnYIESWI0NvwGnOe7RMJzfg6RKjv09_7mYdindHH-7hNBdd_KOFvY-jTr9syjA6eD1XItyXGODgs9XZQh9gf4hxgDoMcE4-1MwRZnuwptgBJqtN8ZUfY_AlpqV81DnDPFUgxdGWdHwLXjt9yPbd_30Gvl1efN1dN7efr252H2-bHrdSNh1mwnW9MAPCUsuOGMMksl3HNRe9sUS6Tg4tp9SxdnDYSNQTYoQbNOsZEvQMfFh7pxQfZpuL2sc5hfpSEYy5ZFQwWSm6UibFnJN1akq-SjgqjNSiWi2q1aJaraqVYDXVrCmfi_39HKnuFBe1V336vlOUE_6jvbtSXyq_Xfl-3L_owT8aQJNM</recordid><startdate>201209</startdate><enddate>201209</enddate><creator>Evans, K</creator><creator>Ackloo, S</creator><creator>Chen, J</creator><creator>Dharsee, M</creator><creator>Li, J</creator><creator>Paulsen, J S</creator><creator>Sills, T</creator><creator>Vaccarino, A</creator><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope></search><sort><creationdate>201209</creationdate><title>F10 Quantifying putative biomarkers of Huntington disease in blood and urine by selected reaction monitoring mass spectrometry</title><author>Evans, K ; Ackloo, S ; Chen, J ; Dharsee, M ; Li, J ; Paulsen, J S ; Sills, T ; Vaccarino, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1499-8157f8b7cd019a982cc590e886a67bce29f89d4633f54df1c90b22c7fda5b5073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Biomarkers</topic><topic>Huntingtons disease</topic><topic>Mass spectrometry</topic><topic>mass spectrometry (MS)</topic><topic>protein biomarkers</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Scientific imaging</topic><topic>selected reaction monitoring (SRM)</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Evans, K</creatorcontrib><creatorcontrib>Ackloo, S</creatorcontrib><creatorcontrib>Chen, J</creatorcontrib><creatorcontrib>Dharsee, M</creatorcontrib><creatorcontrib>Li, J</creatorcontrib><creatorcontrib>Paulsen, J S</creatorcontrib><creatorcontrib>Sills, T</creatorcontrib><creatorcontrib>Vaccarino, A</creatorcontrib><creatorcontrib>and the and PREDICT-HD Investigators and Coordinators</creatorcontrib><collection>Istex</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><jtitle>Journal of neurology, neurosurgery and psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Evans, K</au><au>Ackloo, S</au><au>Chen, J</au><au>Dharsee, M</au><au>Li, J</au><au>Paulsen, J S</au><au>Sills, T</au><au>Vaccarino, A</au><aucorp>and the and PREDICT-HD Investigators and Coordinators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>F10 Quantifying putative biomarkers of Huntington disease in blood and urine by selected reaction monitoring mass spectrometry</atitle><jtitle>Journal of neurology, neurosurgery and psychiatry</jtitle><addtitle>J Neurol Neurosurg Psychiatry</addtitle><date>2012-09</date><risdate>2012</risdate><volume>83</volume><issue>Suppl 1</issue><spage>A24</spage><epage>A24</epage><pages>A24-A24</pages><issn>0022-3050</issn><eissn>1468-330X</eissn><abstract>BackgroundAlthough the gene expansion associated with Huntington Disease (HD) is well known, the downstream effects are complex and poorly understood. Delineating molecular pathways that become disrupted in the presence of an expanded repeat protein will provide insight into the relationship between the expression of proteins and underlying pathophysiology, and begin to point the way to tailored therapeutics.AimsProtein biomarkers can be sourced from bodily fluids, including blood plasma and urine, and may identify presence of disease, either before or after the appearance of signs or symptoms. The aim of the present study was to systematically profile protein expression in HD-expanded individuals, and relate these findings to metrics of disease severity.MethodsWe applied selected reaction monitoring (SRM) mass spectrometry (MS) proteomic profiling techniques to analyse samples from HD gene-expansion individuals that participated in PREDICT-HD. Plasma and urine samples, along with corresponding UHDRS Motor subscale scores, were supplied from 10 male HD motor manifest gene-expansion carriers (CAG repeat length >36; UHDRS Diagnostic Confidence Level >3) and 10 age-matched male controls (non-gene-expanded family members). Samples were collected as part of the PREDICT-HD protocol.ResultsCandidate proteins were identified to be differentially expressed in HD gene-expansion carriers relative to non-expanded familial controls. Moreover, within gene-expansion carriers, a sub-set of proteins were identified that were correlated with severity of motor manifestations, and may represent potential biomarkers of disease severity. Preliminary investigations using pooled specimens from these same patients revealed that some proteins showing differential expression in plasma appear to show similar differences in urine.ConclusionsUsing proteomic profiling techniques we have identified proteins showing differential expression in relation to HD, many of which to our knowledge have never before been measured in plasma. The identification of biomarkers through the use of SRM-MS holds great promise to increasing our understanding of HD.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd</pub><doi>10.1136/jnnp-2012-303524.75</doi></addata></record> |
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subjects | Biomarkers Huntingtons disease Mass spectrometry mass spectrometry (MS) protein biomarkers Proteins Proteomics Scientific imaging selected reaction monitoring (SRM) Urine |
title | F10 Quantifying putative biomarkers of Huntington disease in blood and urine by selected reaction monitoring mass spectrometry |
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