Serum neurofilament light chain in FTLD: association with C9orf72, clinical phenotype, and prognosis

Abstract

ObjectiveThe aim of the present study was to compare the levels of serum neurofilament light chain (sNfL) in frontotemporal lobar degeneration (FTLD) patients of different clinical subtypes (bvFTD, PPA, and FTLD‐MND) and with or without the C9orf72 repeat expansion, and to correlate sNfL levels to disease progression, assessed by the brain atrophy rate and survival time.MethodsThe sNfL levels were determined from 78 FTLD patients (C9orf72 repeat expansion carriers [n = 26] and non‐carriers [n = 52]) with Single Molecule Array (SIMOA). The progression of brain atrophy was evaluated using repeated T1‐weighted MRI scans and the survival time from medical records.ResultsIn the total FTLD cohort, sNfL levels were significantly higher in C9orf72 repeat expansion carriers compared to non‐carriers. Considering clinical phenotypes, sNfL levels were higher in the C9orf72 repeat expansion carriers than in the non‐carriers in bvFTD and PPA groups. Furthermore, sNfL levels were the highest in the FTLD‐MND group (median 105 pg/mL) and the lowest in the bvFTD group (median 27 pg/mL). Higher sNfL levels significantly correlated with frontal cortical atrophy rate and subcortical grey matter atrophy rate. The higher sNfL levels also associated with shorter survival time.InterpretationOur results indicate that the C9orf72 repeat expansion carriers show elevated sNFL levels compared to non‐carriers and that the levels differ among different clinical phenotypes of FTLD. Higher sNfL levels correlated with a shorter survival time and cortical and subcortical atrophy rates. Thus, sNfL could prove as a potential prognostic biomarker in FTLD.

Blood Biomarkers in Frontotemporal Dementia: Review and Meta-Analysis

“…There are limited number of studies comparing p-Tau181 between AD and FTD. Apart from p-Tau181, p-Tau217 has also been investigated both in CSF [ 51 ] and in plasma [ 52 ]. From these findings, plasma p-Tau217 differentiated AD from FTD and other neurodegenerative diseases, and may show higher accuracy than p-Tau181.…”

Predictors of survival in frontotemporal lobar degeneration syndromes

“…68 The invasive nature and reduced patient acceptability of lumbar puncture has led to interest in blood-based assays for the quantification of NfL, which are highly correlated with CSF levels, and have similarly been shown to correlate with disease severity and predict survival in FTLD. 69,70,71,72 Tau CSF tau is another biomarker with growing utility in the diagnosis and prediction of survival in dementia syndromes, with particularly robust evidence in AD. 73 Results of tau levels in FTLD are more variable, potentially due to the heterogenous neuropathology of FTLD (e.g.…”

Cerebrospinal Fluid and Blood Neurofilament Light Chain Protein in Prion Disease and Other Rapidly Progressive Dementias: Current State of the Art

“…In this regard, few studies showed an association between high CSF NfL levels and rapid cognitive decline in AD's mild cognitive impairment stage (Zetterberg et al, 2016;Pillai et al, 2020). Similarly, in the FTD spectrum, higher basal CSF and/or blood NfL values have been related to faster disease progression (in some clinical syndromes) (Ljubenkov et al, 2018;Rojas et al, 2018) and shorter survival (Meeter et al, 2018;van der Ende et al, 2019;Benussi et al, 2020;Cajanus et al, 2020), suggesting the utility of an early NfL assessment in the prediction of future disease aggressiveness.…”