DOI: 10.1002/alz.082525 ISSN: 1552-5260

Association of novel CSF biomarker candidates with cortical thickness in genetic frontotemporal dementia

Abbe Ullgren, Sofia Bergström, Melissa T. Rydell, Linn Öijerstedt, Julia Remnestål, Jennie Olofsson, Harro Seelaar, John C. van Swieten, Matthis Synofzik, Raquel Sanchez‐Valle, Fermin Moreno, Elizabeth Finger, Mario Masellis, Carmela Tartaglia, Rik Vandenberghe, Daniela Galimberti, Barbara Borroni, Christopher Butler, Isabelle Le Ber, Alexander Gerhard, Simon Ducharme, Robert Laforce, Jonathan D. Rohrer, Elena Rodriguez‐Vieitez, Anna Månberg, Peter Nilsson, Caroline Graff,
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



A novel panel of 14 proteins measured in the CSF could separate individuals with genetic frontotemporal dementia (FTD) from controls, with most significant findings observed for neurofilament medium (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4) [1]. However, it is currently unknown whether these altered protein levels in the CSF reflect neurodegenerative changes in the brain. The aim of this study was to explore the cross‐sectional associations between the previously identified CSF biomarker candidates and cortical thickness in presymptomatic and symptomatic mutation carriers, and whether those associations differ by FTD mutation type.


We have analyzed T1 MRI scans alongside concurrent CSF samples from 202 individuals from the GENFI cohort, belonging to families that carry FTD mutations in either C9orf72, GRN or MAPT genes. The study sample included symptomatic mutation carriers, presymptomatic mutation carriers and non‐carrier controls. Cortical thickness was estimated with FreeSurfer and CSF protein levels were measured via a multiplexed antibody‐based suspension bead array. The correlations between regional cortical thickness and protein levels were calculated via linear regression.


Altered levels of NEFM, AQP4, APOA1, PTPRN2, CTSS, SERPINA3, C4, AMPH and CD14 were all correlated with increased atrophy of at least one cortical region. Some effects were mutation specific, but NEFM, AQP4 and APOA1 correlated with atrophy in all mutation groups. We also observed mutation specific effects for 10 of the proteins. CTSS levels were only correlated with cortical atrophy in C9orf72 mutation carriers while NPTX2, VGF and PTPRN2 correlated with atrophy in GRN mutation carriers. In MAPT mutation carriers, 6 different proteins correlated with atrophy in the right temporal pole.


The proposed fluid biomarker candidates continue to show promise and further longitudinal studies will contribute to elucidate their relationship to cortical atrophy and their prognostic value in genetic FTD.

[1] Bergström et al. Mol Neurodegener. 2021; 16(1):79

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