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Open Access 01-12-2018 | Research

The CSF neurofilament light signature in rapidly progressive neurodegenerative dementias

Authors: Samir Abu-Rumeileh, Sabina Capellari, Michelangelo Stanzani-Maserati, Barbara Polischi, Paolo Martinelli, Paola Caroppo, Anna Ladogana, Piero Parchi

Published in: Alzheimer's Research & Therapy | Issue 1/2018

Abstract

Background

Neurofilament light chain protein (NfL) is a surrogate biomarker of neurodegeneration that has never been systematically tested, either alone or in combination with other biomarkers, in atypical/rapidly progressive neurodegenerative dementias (NDs).

Methods

Using validated, commercially available enzyme-linked immunosorbent assay kits, we measured cerebrospinal fluid (CSF) NfL, total tau (t-tau), phosphorylated tau, and β-amyloid 42 in subjects with a neuropathological or clinical diagnosis of prion disease (n = 141), Alzheimer’s disease (AD) (n = 73), dementia with Lewy bodies (DLB) (n = 35), or frontotemporal lobar degeneration (FTLD) (n = 44). Several cases with an atypical/rapidly progressive course were included in each group. We evaluated the diagnostic accuracy of every CSF biomarker and their combinations by ROC curve analyses.

Results

In each patient group CSF NfL showed higher levels than in control subjects, reaching the highest values in those with Creutzfeldt-Jakob disease (CJD). In the latter, NfL showed a divergent, subtype-specific correlation with t-tau, depending on the degree of subcortical involvement and disease duration. Most significantly, patients with classic sporadic CJD (sCJD) MM1 showed a significantly lower concentration of CSF NfL than those with sCJD MV2, despite the much higher t-tau levels and the more rapid clinical course. High NfL levels were also detected in most atypical CJD cases, showing a disease duration longer than 2 years and/or borderline/negative results in other CSF assays (e.g., 14-3-3, t-tau, and prion real-time quaking-induced conversion). Rapidly progressive/atypical cases showed higher NfL levels than typical patients in FTLD, but not in AD or DLB. NfL showed accuracy similar to that of t-tau in discriminating CJD from other NDs, but it had higher efficacy in differentiating atypical forms, especially in regard to Alzheimer’s disease.

Conclusions

The present data indicate that CSF NfL and t-tau levels reflect distinct pathophysiological mechanisms of neurodegeneration and support the clinical use of NfL as a fast screening biomarker for the differential diagnosis of atypical/rapidly progressive NDs.

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Title: The CSF neurofilament light signature in rapidly progressive neurodegenerative dementias
Authors: Samir Abu-Rumeileh
Sabina Capellari
Michelangelo Stanzani-Maserati
Barbara Polischi
Paolo Martinelli
Paola Caroppo
Anna Ladogana
Piero Parchi
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2018
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-017-0331-1

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

The CSF neurofilament light signature in rapidly progressive neurodegenerative dementias

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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