TY - JOUR
T1 - Neurofilament light chain: a biomarker for genetic frontotemporal dementia
AU - Meeter, Lieke H.
AU - Dopper, Elise G.
AU - Jiskoot, Lize C.
AU - Sanchez-Valle, Raquel
AU - Graff, Caroline
AU - Benussi, Luisa
AU - Ghidoni, Roberta
AU - Pijnenburg, Yolande A.
AU - Borroni, Barbara
AU - Galimberti, Daniela
AU - Laforce, Robert Jr
AU - Masellis, Mario
AU - Vandenberghe, Rik
AU - Le Ber, Isabelle
AU - Otto, Markus
AU - van Minkelen, Rick
AU - Papma, Janne M.
AU - Rombouts, Serge A.
AU - Balasa, Mircea
AU - Oijerstedt, Linn
AU - Jelic, Vesna
AU - Dick, Katrina M.
AU - Cash, David M.
AU - Harding, Sophie R.
AU - Cardoso, M. Jorge
AU - Ourselin, Sebastien
AU - Rossor, Martin N.
AU - Padovani, Alessandro
AU - Scarpini, Elio
AU - Fenoglio, Chiara
AU - Tartaglia, Maria C.
AU - Lamari, Foudil
AU - Barro, Christian
AU - Kuhle, Jens
AU - Rohrer, Jonathan D.
AU - Teunissen, Charlotte E.
AU - van Swieten, John C.
PY - 2016/8
Y1 - 2016/8
N2 - Objective To evaluate cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL) levels in genetic frontotemporal dementia (FTD) as a potential biomarker in the presymptomatic stage and during the conversion into the symptomatic stage. Additionally, to correlate NfL levels to clinical and neuroimaging parameters. Methods In this multicenter case–control study, we investigated CSF NfL in 174 subjects (48 controls, 40 presymptomatic carriers and 86 patients with microtubule‐associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72) mutations), and serum NfL in 118 subjects (39 controls, 44 presymptomatic carriers, 35 patients). In 55 subjects both CSF and serum was determined. In two subjects CSF was available before and after symptom onset (converters). Additionally, NfL levels were correlated with clinical parameters, survival, and regional brain atrophy. Results CSF NfL levels in patients (median 6762 pg/mL, interquartile range 3186–9309 pg/mL) were strongly elevated compared with presymptomatic carriers (804 pg/mL, 627–1173 pg/mL, P < 0.001), resulting in a good diagnostic performance to discriminate both groups. Serum NfL correlated highly with CSF NfL (rs = 0.87, P < 0.001) and was similarly elevated in patients. Longitudinal samples in the converters showed a three‐ to fourfold increase in CSF NfL after disease onset. Additionally, NfL levels in patients correlated with disease severity, brain atrophy, annualized brain atrophy rate and survival. Interpretation NfL in both serum and CSF has the potential to serve as a biomarker for clinical disease onset and has a prognostic value in genetic FTD.
AB - Objective To evaluate cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL) levels in genetic frontotemporal dementia (FTD) as a potential biomarker in the presymptomatic stage and during the conversion into the symptomatic stage. Additionally, to correlate NfL levels to clinical and neuroimaging parameters. Methods In this multicenter case–control study, we investigated CSF NfL in 174 subjects (48 controls, 40 presymptomatic carriers and 86 patients with microtubule‐associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72) mutations), and serum NfL in 118 subjects (39 controls, 44 presymptomatic carriers, 35 patients). In 55 subjects both CSF and serum was determined. In two subjects CSF was available before and after symptom onset (converters). Additionally, NfL levels were correlated with clinical parameters, survival, and regional brain atrophy. Results CSF NfL levels in patients (median 6762 pg/mL, interquartile range 3186–9309 pg/mL) were strongly elevated compared with presymptomatic carriers (804 pg/mL, 627–1173 pg/mL, P < 0.001), resulting in a good diagnostic performance to discriminate both groups. Serum NfL correlated highly with CSF NfL (rs = 0.87, P < 0.001) and was similarly elevated in patients. Longitudinal samples in the converters showed a three‐ to fourfold increase in CSF NfL after disease onset. Additionally, NfL levels in patients correlated with disease severity, brain atrophy, annualized brain atrophy rate and survival. Interpretation NfL in both serum and CSF has the potential to serve as a biomarker for clinical disease onset and has a prognostic value in genetic FTD.
U2 - https://doi.org/10.1002/acn3.325
DO - https://doi.org/10.1002/acn3.325
M3 - Article
C2 - 27606344
SN - 2328-9503
VL - 3
SP - 623
EP - 636
JO - Annals of clinical and translational neurology
JF - Annals of clinical and translational neurology
IS - 8
ER -