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Alzheimers Res Ther. 2018 Jan 11;10(1):3. doi: 10.1186/s13195-017-0331-1.

The CSF neurofilament light signature in rapidly progressive neurodegenerative dementias.

Author information

1
Department of Biomedical and NeuroMotor Sciences, University of Bologna, 40123, Bologna, Italy.
2
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Institute of Neurological Sciences of Bologna, Bellaria Hospital, 40139, Bologna, Italy.
3
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation "Carlo Besta" Neurological Institute, 20133, Milan, Italy.
4
Department of Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
5
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Institute of Neurological Sciences of Bologna, Bellaria Hospital, 40139, Bologna, Italy. piero.parchi@unibo.it.
6
Department of Diagnostic Experimental and Specialty Medicine (DIMES), University of Bologna, 40138, Bologna, Italy. piero.parchi@unibo.it.

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.

KEYWORDS:

Alzheimer’s disease; Corticobasal syndrome; Creutzfeldt-Jakob disease; Dementia with Lewy bodies; Frontotemporal dementia; Progressive supranuclear palsy

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