Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders

Constance Delaby ,Bessy Benejam ,Laia Muñoz ,Roser Ribosa-Nogué ,Estrella Morenas‐Rodríguez ,Sònia Sirisi ,Isabel Sala Matavera ,Isabel Barroeta ,Daniel Alcolea ,Jordi Clarimón ,Juan Fortea ,Miren Altuna ,Javier Pagonabarraga ,Laura Videla ,Ricard Rojas‐García ,Olivia Belbin ,Andrea Subirana ,Ignacio Illán-Gala ,Sylvain Lehmann ,Miguel A Santos‐Santos ,Rafael Blesa ,Belén Sánchez-Saudinós ,María Carmona-Iragui ,Teresa Estellés ,Janina Turón-Sans ,Alberto Lleó

doi:10.1038/s41598-020-66090-x

Abstract

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

Highlights

Biomarkers of neurodegenerative diseases are key for the evaluation, differential diagnosis and follow-up of patients with cognitive impairment or dementia
We confirm that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-related syndromes show the highest Cerebrospinal fluid (CSF) neurofilament light (NfL) levels followed by Alzheimer disease (AD) and dementia with Lewy bodies (DLB)
In agreement with a recent meta-analysis that included various neurological conditions, our study confirms the overlap of CSF NfL level between various clinical conditions[19], which may limit its use as a diagnostic marker in the clinical routine of cognitive impairment

Summary

Introduction

Biomarkers of neurodegenerative diseases are key for the evaluation, differential diagnosis and follow-up of patients with cognitive impairment or dementia. A large control-case study that included various neurodegenerative disorders confimed the importance of CSF NfL in the evaluation and follow-up of patients with cognitive impairment[16]: in particular, CSF NfL levels were increased in patients with a diagnosis of MCI, AD, FTD or ALS compared to controls, reflecting the intensity of neurodegenerative processes. We investigated CSF NfL in the SPIN cohort[17], which includes a variety of neurodegenerative disorders, such as AD, FTD, ALS, DLB, PSP, CBS and subjects with Down syndrome (DS). This is the first time to our knowledge that such different phenotypes can be compared through a monocentric cohort. This study highlights the potential role of CSF NfL for the early diagnosis (including prodromal stages) and follow-up of DLB patients

Methods

Results

Conclusion