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Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers

Translational Neurodegeneration 2020年第2期9卷 309-321页

作者： Julia Remnestål Linn Oijerstedt Abbe Ullgren Jennie Olofsson Sofia Bergström Kim Kultima Martin Ingelsson lena kilander Mathias Uhlén Anna Månberg Caroline Graff Peter Nilsson Division of Affinity Proteomics Department of Protein ScienceKTH Royal Institute of TechnologySciLifeLabTomtebodavägen 23 AAlpha 217165 SolnaStockholmSweden Swedish FTD Initiative StockholmSweden Division of Neurogeriatrics Centre for Alzheimer ResearchDepartment of NeurobiologyCare Sciences and SocietyKarolinska Institutet17164SolnaSweden Unit for hereditary dementias Theme AgingKarolinska University HospitalStockholmSweden Department of Medical Sciences Clinical ChemistryUppsala UniversityUppsalaSweden Department of Public Health and Caring Sciences GeriatricsUppsala UniversityUppsalaSweden Department of Neuroscience Karolinska InstitutetSolnaSweden

Background The clinical presentations of frontotemporal dementia(FTD)are diverse and overlap with other neurological *** are,as of today,no biomarkers in clinical practice for diagnosing the ***,we aimed to find protein markers in cerebrospinal fluid(CSF)from patients with FTD,presymptomatic mutation carriers and *** 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 *** findings were further examined in an independent cohort including 13 FTD patients,79 patients with Alzheimer’s disease and 18 healthy *** We found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals(PMC and NC)for 26 *** analysis show patterns of separation between unaffected individuals and FTD patients,especially for those with a clinical diagnosis of *** most statistically significant differences in protein levels were found for VGF,TN-R,NPTXR,TMEM132D,PDYN and *** 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 *** main findings were reproduced in the independent *** In this pilot study,we show a separation of FTD patients from unaffected individuals based on protein levels in *** 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.

关键词： Frontotemporal dementia Cerebrospinal fluid Biomarkers Proteomics Antibody suspension bead array

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