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We have previously identified CSF proteins that could separate individuals with genetic FTD from controls. However, it is unknown whether alterations in these CSF protein levels are associated with neurodegenerative processes. The aim of this study was to explore how these CSF biomarker candidates correlate with symptom severity as well as cortical and subcortical atrophy. The levels of fourteen proteins were measured in CSF from 202 individuals, 131 mutation carriers with mutations in\n                    <jats:italic>C9orf72<\/jats:italic>\n                    ,\n                    <jats:italic>GRN<\/jats:italic>\n                    , or\n                    <jats:italic>MAPT<\/jats:italic>\n                    , and 71 controls, in a cross-sectional subset from the GENFI cohort. The association between the levels of these proteins and CDR plus NACC FTLD-NM sum-of-boxes, cortical thickness, and subcortical volumes were estimated in the mutation carriers. Elevated CSF levels of five out of fourteen proteins were associated with an increased CDR score in the mutation carriers. Additionally, elevated levels of three of these proteins, NEFM, PTPRN2 and SERPINA3, were associated with reduced cortical thickness and\/or subcortical volume among all mutation carriers. Some mutation-specific associations were also observed, with SPP1 and CTSS being associated with CDR and atrophy only in\n                    <jats:italic>MAPT<\/jats:italic>\n                    mutation carriers, while NPTX2 was specific for\n                    <jats:italic>GRN<\/jats:italic>\n                    mutation carriers. As indicated by the association to brain atrophy, the proposed fluid biomarker candidates continue to show promise and additional studies will further elucidate their relationship to cortical atrophy in genetic FTD, and their potential as biomarkers for diagnosis, prognosis, and disease staging.\n                  <\/jats:p>","DOI":"10.1007\/s00702-026-03118-y","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T07:00:55Z","timestamp":1771484455000},"page":"2339-2347","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CSF protein biomarkers are associated with atrophy and symptom severity in genetic FTD: a GENFI study"],"prefix":"10.1007","volume":"133","author":[{"given":"Abbe","family":"Ullgren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa 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