Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders.

Katisko K1, Cajanus A1, Jääskeläinen O1, Kontkanen A1, Hartikainen P1,2, Korhonen VE3, Helisalmi S1, Haapasalo A4, Koivumaa-Honkanen H5,6, Herukka SK1,2, Remes AM1,2,7,8, Solje E9,10.

Author information

1: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Yliopistonranta 1C, 1627, 70211, Kuopio, Finland.
2: Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland.
3: Neuro Center, Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
4: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
5: Institute of Clinical Medicine-Psychiatry, University of Eastern Finland, Kuopio, Finland.
6: Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland.
7: MRC Oulu, Oulu University Hospital, Oulu, Finland.
8: Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland.
9: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Yliopistonranta 1C, 1627, 70211, Kuopio, Finland. eino.solje@uef.fi.
10: Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland. eino.solje@uef.fi.

Abstract

Due to the significant clinical overlap between frontotemporal lobar degeneration (FTLD) spectrum disorders and late-onset primary psychiatric disorders (PPD), diagnostic biomarkers reflecting the different underlying pathophysiologies are urgently needed. Thus far, elevated cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) have been reported in various neurological conditions. Furthermore, recent advancements in ultrasensitive analytical methods (e.g., single molecule array, Simoa) have enabled sensitive and less invasive NfL detection also from blood samples. In this study, we evaluated the potential of serum NfL (sNfL) as a diagnostic tool between FTLD and PPD. We analyzed sNfL levels with Simoa from 125 participants including patients from FTLD (n = 91) and PPD (n = 34) spectra. Our results show that sNfL levels are higher in the FTLD group compared to the PPD group as well as in separate clinical subtypes of FTLD compared to different psychiatric manifestations (i.e., mood or psychotic disorders). At single-subject level, discrimination between FTLD and PPD was possible with 80% sensitivity and 85% specificity (AUC = 0.850, 95% CI 0.776-0.923), and between behavioral variant frontotemporal dementia (bvFTD) and PPD with 79% sensitivity and 85% specificity (AUC = 0.830, 95% CI 0.732-0.908). These findings highlight the potential of sNfL as a discriminating biomarker for FTLD over PPD in patients with wide-ranging behavioral, psychiatric and cognitive symptoms.