Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriersShow others and affiliations
2020 (English)In: Translational Neurodegeneration, ISSN 2047-9158, Vol. 9, no 1, article id 27
Article in journal (Refereed) Published
Abstract [en]
Background: The clinical presentations of frontotemporal dementia (FTD) are diverse and overlap with other neurological disorders. There are, as of today, no biomarkers in clinical practice for diagnosing the disorders. Here, we aimed to find protein markers in cerebrospinal fluid (CSF) from patients with FTD, presymptomatic mutation carriers and non-carriers. Methods: Antibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD (bvFTD, n = 16) and progressive primary aphasia (PPA, n = 13), as well as presymptomatic mutation carriers (PMC, n = 16) and non-carriers (NC, n = 8). A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF samples. The findings were further examined in an independent cohort including 13 FTD patients, 79 patients with Alzheimer's disease and 18 healthy controls. Results: We found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals (PMC and NC) for 26 proteins. The analysis show patterns of separation between unaffected individuals and FTD patients, especially for those with a clinical diagnosis of bvFTD. The most statistically significant differences in protein levels were found for VGF, TN-R, NPTXR, TMEM132D, PDYN and NF-M. Patients with FTD were found to have higher levels of TN-R and NF-M, and lower levels of VGF, NPTXR, TMEM132D and PDYN, compared to unaffected individuals. The main findings were reproduced in the independent cohort. Conclusion: In this pilot study, we show a separation of FTD patients from unaffected individuals based on protein levels in CSF. Further investigation is required to explore the CSF profiles in larger cohorts, but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.
Place, publisher, year, edition, pages
Springer Nature , 2020. Vol. 9, no 1, article id 27
Keywords [en]
Frontotemporal dementia, Cerebrospinal fluid, Biomarkers, Proteomics, Antibody suspension bead array
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:kth:diva-278656DOI: 10.1186/s40035-020-00198-yISI: 000544889300001PubMedID: 32576262Scopus ID: 2-s2.0-85087855817OAI: oai:DiVA.org:kth-278656DiVA, id: diva2:1454605
Note
QC 20200717
2020-07-172020-07-172023-12-07Bibliographically approved