Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics
Abstract Introduction Reliable cerebrospinal fluid (CSF) biomarkers enabling identification of frontotemporal dementia (FTD) and its pathologic subtypes are lacking. Methods Unbiased high-resolution mass spectrometry–based proteomics was applied on CSF of FTD patients with TAR DNA-binding protein 43...
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| creator | Teunissen, Charlotte E Elias, Naura Koel-Simmelink, Marleen J.A Durieux-Lu, Sisi Malekzadeh, Arjan Pham, Thang V Piersma, Sander R Beccari, Tommaso Meeter, Lieke H.H Dopper, Elise G.P van Swieten, John C Jimenez, Connie R Pijnenburg, Yolande A.L |
| description | Abstract Introduction Reliable cerebrospinal fluid (CSF) biomarkers enabling identification of frontotemporal dementia (FTD) and its pathologic subtypes are lacking. Methods Unbiased high-resolution mass spectrometry–based proteomics was applied on CSF of FTD patients with TAR DNA-binding protein 43 (TDP-43, FTD-TDP, n = 12) or tau pathology (FTD-tau, n = 8), and individuals with subjective memory complaints (SMC, n = 10). Validation was performed by applying enzyme-linked immunosorbent assay (ELISA) or enzymatic assays, when available, in a larger cohort (FTLD-TDP, n = 21, FTLD-tau, n = 10, SMC, n = 23) and in Alzheimer's disease (n = 20), dementia with Lewy bodies (DLB, n = 20), and vascular dementia (VaD, n = 18). Results Of 1914 identified CSF proteins, 56 proteins were differentially regulated (fold change >1.2, P |
| doi_str_mv | 10.1016/j.dadm.2015.12.004 |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4879654</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S2352872915000974</els_id><sourcerecordid>1792775068</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5404-78eaa51a29ee5e1f698c1af90edc08eb009b0d09fd856d0fd017470f91c998773</originalsourceid><addsrcrecordid>eNqNUk1v1DAUjBCIVqV_gAOKxIXLhmdvHMcSqlRaPlXgAJwtx37eepvEwU4WrfjzOEpZlR4QF9uyZ8bz3rwse0qgIECql9vCKNMVFAgrCC0AygfZMV0zuqo5FQ_vnI-y0xi3AEBKQUsCj7MjyulasLU4zn599jtsc-PUpvdxdDrXGLAJPg6uV21u28mZvHG-U-EGQ8ytD_mgxmvf-k1Cx6kZ9wPG3NvcBt-PfsRu8CFRDXbYj07lzsy7dZiE9vkQEsR3Tscn2SOr2oint_tJ9v3tm28X71dXX959uDi_WmlWQrniNSrFiKICkSGxlag1UVYAGg01NgCiAQPCmppVBqwBwksOVhAtRM35-iQ7W3SHqekSKblJ_uQQXCpqL71y8u-X3l3Ljd_JsuaiYmUSeHErEPyPCeMoOxc1tq3q0U9REi4o5wyqOkGf34Nu_RRSJ6OkjFFSVlSIhKILSqdGx4D2YIaAnOOVWznHK-d4JaEyxZtIz-6WcaD8CTMBXi-An67F_X9IysvzS_oxLZ_mS0KXX14tIpgS2TkMMmqHvUbjAupRGu_-bfLsHl23rndatTe4x3hoBpExEeTXeUrnISUsDajg5fo3asPiYw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2552146299</pqid></control><display><type>article</type><title>Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics</title><source>Wiley Online Library - AutoHoldings Journals</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Online Library (Open Access Collection)</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Teunissen, Charlotte E ; Elias, Naura ; Koel-Simmelink, Marleen J.A ; Durieux-Lu, Sisi ; Malekzadeh, Arjan ; Pham, Thang V ; Piersma, Sander R ; Beccari, Tommaso ; Meeter, Lieke H.H ; Dopper, Elise G.P ; van Swieten, John C ; Jimenez, Connie R ; Pijnenburg, Yolande A.L</creator><creatorcontrib>Teunissen, Charlotte E ; Elias, Naura ; Koel-Simmelink, Marleen J.A ; Durieux-Lu, Sisi ; Malekzadeh, Arjan ; Pham, Thang V ; Piersma, Sander R ; Beccari, Tommaso ; Meeter, Lieke H.H ; Dopper, Elise G.P ; van Swieten, John C ; Jimenez, Connie R ; Pijnenburg, Yolande A.L</creatorcontrib><description>Abstract Introduction Reliable cerebrospinal fluid (CSF) biomarkers enabling identification of frontotemporal dementia (FTD) and its pathologic subtypes are lacking. Methods Unbiased high-resolution mass spectrometry–based proteomics was applied on CSF of FTD patients with TAR DNA-binding protein 43 (TDP-43, FTD-TDP, n = 12) or tau pathology (FTD-tau, n = 8), and individuals with subjective memory complaints (SMC, n = 10). Validation was performed by applying enzyme-linked immunosorbent assay (ELISA) or enzymatic assays, when available, in a larger cohort (FTLD-TDP, n = 21, FTLD-tau, n = 10, SMC, n = 23) and in Alzheimer's disease (n = 20), dementia with Lewy bodies (DLB, n = 20), and vascular dementia (VaD, n = 18). Results Of 1914 identified CSF proteins, 56 proteins were differentially regulated (fold change >1.2, P < .05) between the different patient groups: either between the two pathologic subtypes (10 proteins), or between at least one of these FTD subtypes and SMC (47 proteins). We confirmed the differential expression of YKL-40 by ELISA in a partly independent cohort. Furthermore, enzyme activity of catalase was decreased in FTD subtypes compared with SMC. Further validation in a larger cohort showed that the level of YKL-40 was twofold increased in both FTD pathologic subtypes compared with SMC and that the levels in FTLD-tau were higher compared to Alzheimer's dementia (AD), DLB, and VaD patients. Clinical validation furthermore showed that the catalase enzyme activity was decreased in the FTD subtypes compared to SMC, AD and DLB. Discussion We identified promising CSF biomarkers for both FTD differential diagnosis and pathologic subtyping. YKL-40 and catalase enzyme activity should be validated further in similar pathology defined patient cohorts for their use for FTD diagnosis or treatment development.</description><identifier>ISSN: 2352-8729</identifier><identifier>EISSN: 2352-8729</identifier><identifier>DOI: 10.1016/j.dadm.2015.12.004</identifier><identifier>PMID: 27239539</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alzheimer's disease ; Biobanks ; Biomarkers ; Cerebrospinal fluid ; CSF Biomarkers ; Dementia ; Differential diagnosis ; Enzymes ; Fatty acids ; Frontotemporal dementia ; Immunoassay ; Laboratories ; Medical diagnosis ; Memory ; Mental disorders ; Mutation ; Neurology ; Older people ; Other ; Pathology ; Patients ; Proteins ; Proteomics ; Standard deviation ; Tau ; TDP-43</subject><ispartof>Alzheimer's & dementia : diagnosis, assessment & disease monitoring, 2016, Vol.2 (1), p.86-94</ispartof><rights>The Authors</rights><rights>2016 The Authors</rights><rights>2016 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.</rights><rights>2016. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 The Authors 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5404-78eaa51a29ee5e1f698c1af90edc08eb009b0d09fd856d0fd017470f91c998773</citedby><cites>FETCH-LOGICAL-c5404-78eaa51a29ee5e1f698c1af90edc08eb009b0d09fd856d0fd017470f91c998773</cites><orcidid>0000-0003-4277-0815 ; 0000-0002-4061-0837 ; 0000-0001-9637-6579</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879654/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879654/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1418,4025,11567,27928,27929,27930,45579,45580,46057,46481,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27239539$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teunissen, Charlotte E</creatorcontrib><creatorcontrib>Elias, Naura</creatorcontrib><creatorcontrib>Koel-Simmelink, Marleen J.A</creatorcontrib><creatorcontrib>Durieux-Lu, Sisi</creatorcontrib><creatorcontrib>Malekzadeh, Arjan</creatorcontrib><creatorcontrib>Pham, Thang V</creatorcontrib><creatorcontrib>Piersma, Sander R</creatorcontrib><creatorcontrib>Beccari, Tommaso</creatorcontrib><creatorcontrib>Meeter, Lieke H.H</creatorcontrib><creatorcontrib>Dopper, Elise G.P</creatorcontrib><creatorcontrib>van Swieten, John C</creatorcontrib><creatorcontrib>Jimenez, Connie R</creatorcontrib><creatorcontrib>Pijnenburg, Yolande A.L</creatorcontrib><title>Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics</title><title>Alzheimer's & dementia : diagnosis, assessment & disease monitoring</title><addtitle>Alzheimers Dement (Amst)</addtitle><description>Abstract Introduction Reliable cerebrospinal fluid (CSF) biomarkers enabling identification of frontotemporal dementia (FTD) and its pathologic subtypes are lacking. Methods Unbiased high-resolution mass spectrometry–based proteomics was applied on CSF of FTD patients with TAR DNA-binding protein 43 (TDP-43, FTD-TDP, n = 12) or tau pathology (FTD-tau, n = 8), and individuals with subjective memory complaints (SMC, n = 10). Validation was performed by applying enzyme-linked immunosorbent assay (ELISA) or enzymatic assays, when available, in a larger cohort (FTLD-TDP, n = 21, FTLD-tau, n = 10, SMC, n = 23) and in Alzheimer's disease (n = 20), dementia with Lewy bodies (DLB, n = 20), and vascular dementia (VaD, n = 18). Results Of 1914 identified CSF proteins, 56 proteins were differentially regulated (fold change >1.2, P < .05) between the different patient groups: either between the two pathologic subtypes (10 proteins), or between at least one of these FTD subtypes and SMC (47 proteins). We confirmed the differential expression of YKL-40 by ELISA in a partly independent cohort. Furthermore, enzyme activity of catalase was decreased in FTD subtypes compared with SMC. Further validation in a larger cohort showed that the level of YKL-40 was twofold increased in both FTD pathologic subtypes compared with SMC and that the levels in FTLD-tau were higher compared to Alzheimer's dementia (AD), DLB, and VaD patients. Clinical validation furthermore showed that the catalase enzyme activity was decreased in the FTD subtypes compared to SMC, AD and DLB. Discussion We identified promising CSF biomarkers for both FTD differential diagnosis and pathologic subtyping. YKL-40 and catalase enzyme activity should be validated further in similar pathology defined patient cohorts for their use for FTD diagnosis or treatment development.</description><subject>Alzheimer's disease</subject><subject>Biobanks</subject><subject>Biomarkers</subject><subject>Cerebrospinal fluid</subject><subject>CSF Biomarkers</subject><subject>Dementia</subject><subject>Differential diagnosis</subject><subject>Enzymes</subject><subject>Fatty acids</subject><subject>Frontotemporal dementia</subject><subject>Immunoassay</subject><subject>Laboratories</subject><subject>Medical diagnosis</subject><subject>Memory</subject><subject>Mental disorders</subject><subject>Mutation</subject><subject>Neurology</subject><subject>Older people</subject><subject>Other</subject><subject>Pathology</subject><subject>Patients</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Standard 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identified by proteomics</title><author>Teunissen, Charlotte E ; Elias, Naura ; Koel-Simmelink, Marleen J.A ; Durieux-Lu, Sisi ; Malekzadeh, Arjan ; Pham, Thang V ; Piersma, Sander R ; Beccari, Tommaso ; Meeter, Lieke H.H ; Dopper, Elise G.P ; van Swieten, John C ; Jimenez, Connie R ; Pijnenburg, Yolande A.L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5404-78eaa51a29ee5e1f698c1af90edc08eb009b0d09fd856d0fd017470f91c998773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alzheimer's disease</topic><topic>Biobanks</topic><topic>Biomarkers</topic><topic>Cerebrospinal fluid</topic><topic>CSF Biomarkers</topic><topic>Dementia</topic><topic>Differential diagnosis</topic><topic>Enzymes</topic><topic>Fatty acids</topic><topic>Frontotemporal dementia</topic><topic>Immunoassay</topic><topic>Laboratories</topic><topic>Medical diagnosis</topic><topic>Memory</topic><topic>Mental 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A.L</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>PubMed</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>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>ProQuest One 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teunissen, Charlotte E</au><au>Elias, Naura</au><au>Koel-Simmelink, Marleen J.A</au><au>Durieux-Lu, Sisi</au><au>Malekzadeh, Arjan</au><au>Pham, Thang V</au><au>Piersma, Sander R</au><au>Beccari, Tommaso</au><au>Meeter, Lieke H.H</au><au>Dopper, Elise G.P</au><au>van Swieten, John C</au><au>Jimenez, Connie R</au><au>Pijnenburg, Yolande A.L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics</atitle><jtitle>Alzheimer's & dementia : diagnosis, assessment & disease monitoring</jtitle><addtitle>Alzheimers Dement (Amst)</addtitle><date>2016</date><risdate>2016</risdate><volume>2</volume><issue>1</issue><spage>86</spage><epage>94</epage><pages>86-94</pages><issn>2352-8729</issn><eissn>2352-8729</eissn><abstract>Abstract Introduction Reliable cerebrospinal fluid (CSF) biomarkers enabling identification of frontotemporal dementia (FTD) and its pathologic subtypes are lacking. Methods Unbiased high-resolution mass spectrometry–based proteomics was applied on CSF of FTD patients with TAR DNA-binding protein 43 (TDP-43, FTD-TDP, n = 12) or tau pathology (FTD-tau, n = 8), and individuals with subjective memory complaints (SMC, n = 10). Validation was performed by applying enzyme-linked immunosorbent assay (ELISA) or enzymatic assays, when available, in a larger cohort (FTLD-TDP, n = 21, FTLD-tau, n = 10, SMC, n = 23) and in Alzheimer's disease (n = 20), dementia with Lewy bodies (DLB, n = 20), and vascular dementia (VaD, n = 18). Results Of 1914 identified CSF proteins, 56 proteins were differentially regulated (fold change >1.2, P < .05) between the different patient groups: either between the two pathologic subtypes (10 proteins), or between at least one of these FTD subtypes and SMC (47 proteins). We confirmed the differential expression of YKL-40 by ELISA in a partly independent cohort. Furthermore, enzyme activity of catalase was decreased in FTD subtypes compared with SMC. Further validation in a larger cohort showed that the level of YKL-40 was twofold increased in both FTD pathologic subtypes compared with SMC and that the levels in FTLD-tau were higher compared to Alzheimer's dementia (AD), DLB, and VaD patients. Clinical validation furthermore showed that the catalase enzyme activity was decreased in the FTD subtypes compared to SMC, AD and DLB. Discussion We identified promising CSF biomarkers for both FTD differential diagnosis and pathologic subtyping. YKL-40 and catalase enzyme activity should be validated further in similar pathology defined patient cohorts for their use for FTD diagnosis or treatment development.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27239539</pmid><doi>10.1016/j.dadm.2015.12.004</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4277-0815</orcidid><orcidid>https://orcid.org/0000-0002-4061-0837</orcidid><orcidid>https://orcid.org/0000-0001-9637-6579</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Alzheimer's disease Biobanks Biomarkers Cerebrospinal fluid CSF Biomarkers Dementia Differential diagnosis Enzymes Fatty acids Frontotemporal dementia Immunoassay Laboratories Medical diagnosis Memory Mental disorders Mutation Neurology Older people Other Pathology Patients Proteins Proteomics Standard deviation Tau TDP-43 |
| title | Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics |
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