Neurofilament light chain cannot be measured in urine to distinguish frontotemporal dementia with primary psychiatric diseases

Abstract

AbstractBackgroundClinical overlap of the behavioral variant of FTD and primary psychiatric diseases (PPD) hampers diagnostic distinction, leading to frequent misdiagnosis and diagnostic delay. NfL in CSF and blood has shown great potential to accurately distinguish bvFTD from PPD and controls. Measurement of NfL in urine would be a minimal invasive, patient‐friendly biomarker assessment and thereby beneficial for future clinical implementation. We aimed to evaluate the diagnostic value of urine NfL concentration to distinguish bvFTD from PPD and controls and to assess if urine and serum NfL levels correlate.Method55 subjects (n = 19 FTD, n = 19 psychiatric patients: functional neurologic disorder n =2; obsessive compulsive disorder n= 1; unspecified mental disorder n =1; bipolar disorder, depressive phase n =1; depression, n = 6; adjustment disorder n = 3; anxiety disorder n = 1; autism spectrum disorder n =1; personality disorder n =2; somatic symptom disorder n = 2, and n = 17 controls) were included with available paired urine and serum samples. All subjects underwent standardized extensive diagnostic assessment. Samples were analyzed with the ultrasensitive SIMOA NfL assay. NfL group comparisons were performed adjusted for age and sex.ResultsIn the majority of the cohort NfL concentrations were not detectable in urine (n = 6 samples above lower limit of detection (0.038 pg/ml): n = 5 FTD, n =1 PPD). The frequency of a detectable NfL level in urine in the FTD (5/19) group did not differ from PPD (1/19); Fisher Exact‐test p = 0.180). In the individuals with detectable urine NfL values there was no correlation between the urine and serum NfL levels. As expected, serum NfL levels were higher in bvFTD compared to psychiatric patients and controls (p < 0.000), adjusted for age and sex.ConclusionOur results implicate that using urine as matrix for NfL analysis is not suitable.