Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration.
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-β1-42 (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.


CONCLUSIONS
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.
Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Carole S
CS
Scherling
Tracey
T
Hall
Flora
F
Berisha
Kristen
K
Klepac
Anna
A
Karydas
Giovanni
G
Coppola
Joel H
JH
Kramer
Gil
G
Rabinovici
Michael
M
Ahlijanian
Bruce L
BL
Miller
William
W
Seeley
Lea T
LT
Grinberg
Howard
H
Rosen
Jere
J
Meredith
Adam L
AL
Boxer
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D012720:Severity of Illness Index
D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L