Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers
Autor: | Lena Kilander, Julia Remnestål, Kim Kultima, Peter Nilsson, Jennie Olofsson, Linn Öijerstedt, Sofia Bergström, Mathias Uhlén, Abbe Ullgren, Martin Ingelsson, Anna Månberg, Caroline Graff |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Oncology Male Proteomics Neurology Neurologi Pilot Projects Disease medicine.disease_cause lcsh:RC346-429 Cohort Studies 0302 clinical medicine Cerebrospinal fluid Mutation biology Cerebrospinal Fluid Proteins Middle Aged Frontotemporal Dementia Cohort Female Antibody Frontotemporal dementia Neurovetenskaper Adult medicine.medical_specialty Heterozygote Cognitive Neuroscience Prodromal Symptoms 03 medical and health sciences Cellular and Molecular Neuroscience Internal medicine mental disorders medicine Humans In patient Genetic Testing lcsh:Neurology. Diseases of the nervous system Aged business.industry Research Neurosciences medicine.disease 030104 developmental biology biology.protein Neurology (clinical) business Antibody suspension bead array 030217 neurology & neurosurgery Biomarkers |
Zdroj: | Translational Neurodegeneration Translational Neurodegeneration, Vol 9, Iss 1, Pp 1-13 (2020) |
Popis: | BackgroundThe 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.MethodsAntibody 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.ResultsWe 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.ConclusionIn 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. |
Databáze: | OpenAIRE |
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