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Protein abundances were compared between these groups. Proteins were then selected for validation if identified by \u22654 peptides and if fold change was \u22640.5 or \u22652.0. Validation and absolute quantification by parallel reaction monitoring (\n PRM<\/jats:styled-content>\n ), a high\u2010resolution targeted\n MS<\/jats:styled-content>\n method, was performed on an international cohort (\n n<\/jats:italic>\n \u00a0=\u00a0210) of presymptomatic and symptomatic\n \n GRN<\/jats:styled-content>\n , C9orf72\n <\/jats:italic>\n and\n \n MAPT<\/jats:styled-content>\n <\/jats:italic>\n mutation carriers.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Unbiased\n MS<\/jats:styled-content>\n revealed 20 differentially abundant proteins between symptomatic mutation carriers and noncarriers and nine between symptomatic and presymptomatic carriers. Seven of these proteins fulfilled our criteria for validation.\n PRM<\/jats:styled-content>\n analyses revealed that symptomatic\n \n GRN<\/jats:styled-content>\n <\/jats:italic>\n mutation carriers had significantly lower levels of neuronal pentraxin receptor (\n NPTXR<\/jats:styled-content>\n ), receptor\u2010type tyrosine\u2010protein phosphatase N2 (\n PTPRN<\/jats:styled-content>\n 2), neurosecretory protein\n VGF<\/jats:styled-content>\n , chromogranin\u2010A (\n CHGA<\/jats:styled-content>\n ), and V\u2010set and transmembrane domain\u2010containing protein 2B (\n VSTM<\/jats:styled-content>\n 2B) than presymptomatic carriers and noncarriers. Symptomatic\n C9orf72<\/jats:italic>\n mutation carriers had lower levels of\n NPTXR<\/jats:styled-content>\n ,\n PTPRN<\/jats:styled-content>\n 2,\n CHGA<\/jats:styled-content>\n , and\n VSTM<\/jats:styled-content>\n 2B than noncarriers, while symptomatic\n \n MAPT<\/jats:styled-content>\n <\/jats:italic>\n mutation carriers had lower levels of\n NPTXR<\/jats:styled-content>\n and\n CHGA<\/jats:styled-content>\n than noncarriers.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n We identified and validated five novel\n CSF<\/jats:styled-content>\n biomarkers in\n \n GRN<\/jats:styled-content>\n \u2010\n <\/jats:italic>\n associated\n FTD<\/jats:styled-content>\n . Our results show that synaptic, secretory vesicle, and inflammatory proteins are dysregulated in the symptomatic stage and may provide new insights into the pathophysiology of genetic FTD. Further validation is needed to investigate their clinical applicability as diagnostic or monitoring biomarkers.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/acn3.745","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T01:30:33Z","timestamp":1552008633000},"page":"698-707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Novel\n CSF<\/scp>\n biomarkers in genetic frontotemporal dementia identified by proteomics"],"prefix":"10.1002","volume":"6","author":[{"given":"Emma L.","family":"van der Ende","sequence":"first","affiliation":[{"name":"Department of Neurology Erasmus Medical Center PO Box\u00a02040 3015 GD Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieke H.","family":"Meeter","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus Medical Center PO Box\u00a02040 3015 GD Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Stingl","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro\u2010oncology Clinical and Cancer Proteomics Department of Neurology Erasmus Medical Center PO Box\u00a02040 3000 CA Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen G. 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