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
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