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Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration
Author(s) -
Scherling Carole S.,
Hall Tracey,
Berisha Flora,
Klepac Kristen,
Karydas Anna,
Coppola Giovanni,
Kramer Joel H.,
Rabinovici Gil,
Ahlijanian Michael,
Miller Bruce L.,
Seeley William,
Grinberg Lea T.,
Rosen Howard,
Meredith Jere,
Boxer Adam L.
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24052
Subject(s) - frontotemporal dementia , pathology , progressive supranuclear palsy , cerebrospinal fluid , frontotemporal lobar degeneration , medicine , psychology , corticobasal degeneration , biomarker , semantic dementia , dementia , oncology , atrophy , disease , biochemistry , chemistry
Objective Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders, including frontotemporal degeneration (FTD). We investigated the clinical correlates of elevated CSF NfL levels in FTD. Methods CSF NfL, amyloid‐β 1–42 (Aβ42), tau, and phosphorylated tau concentrations were compared in 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) of FTD‐causing mutations, and 79 FTD (45 behavioral variant frontotemporal dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic dementia [SD]), 22 progressive supranuclear palsy, 50 Alzheimer disease, 6 Parkinson disease, and 17 corticobasal syndrome patients. Correlations between CSF analyte levels were performed with neuropsychological measures and the Clinical Dementia Rating scale sum of boxes (CDRsb). Voxel‐based morphometry of structural magnetic resonance images determined the relationship between brain volume and CSF NfL. Results Mean CSF NfL concentrations were higher in bvFTD, SD, and PNFA than other groups. NfL in NC2 was similar to NC. CSF NfL, but not other CSF measures, correlated with CDRsb and neuropsychological measures in FTD, but not in other diagnostic groups. Analyses in 2 independent FTD cohorts and a group of autopsy‐verified or biomarker‐enriched cases confirmed the larger group analysis. In FTD, gray and white matter volume negatively correlated with CSF NfL concentration, such that individuals with the highest NfL levels exhibited the most atrophy. Interpretation CSF NfL is elevated in symptomatic FTD and correlates with disease severity. This measurement may be a useful surrogate endpoint of disease severity in FTD clinical trials. Longitudinal studies of CSF NfL in FTD are warranted. ANN NEUROL 2014;75:116–126