Neurofilament light chain: a biomarker for genetic frontotemporal dementia

Lieke H. Meeter; Elise G. Dopper; Lize C. Jiskoot; Raquel Sanchez-Valle; Caroline Graff; Luisa Benussi; Roberta Ghidoni; Yolande A. Pijnenburg; Barbara Borroni; Daniela Galimberti; Robert Jr Laforce; Mario Masellis; Rik Vandenberghe; Isabelle Le Ber; Markus Otto; Rick van Minkelen; Janne M. Papma; Serge A. Rombouts; Mircea Balasa; Linn Öijerstedt; Vesna Jelic; Katrina M. Dick; David M. Cash; Sophie R. Harding; M. Jorge Cardoso; Sebastien Ourselin; Martin N. Rossor; Alessandro Padovani; Elio Scarpini; Chiara Fenoglio; Maria C. Tartaglia; Foudil Lamari; Christian Barro; Jens Kuhle; Jonathan D. Rohrer; Charlotte E. Teunissen; John C. van Swieten

doi:10.1002/acn3.325

Neurofilament light chain: a biomarker for genetic frontotemporal dementia

Lieke H. Meeter, Elise G. Dopper, Lize C. Jiskoot, Raquel Sanchez-Valle, Caroline Graff, Luisa Benussi, Roberta Ghidoni, Yolande A. Pijnenburg, Barbara Borroni, Daniela Galimberti, Robert Jr Laforce, Mario Masellis, Rik Vandenberghe, Isabelle Le Ber, Markus Otto, Rick van Minkelen, Janne M. Papma, Serge A. Rombouts, Mircea Balasa, Linn ÖijerstedtVesna Jelic, Katrina M. Dick, David M. Cash, Sophie R. Harding, M. Jorge Cardoso, Sebastien Ourselin, Martin N. Rossor, Alessandro Padovani, Elio Scarpini, Chiara Fenoglio, Maria C. Tartaglia, Foudil Lamari, Christian Barro, Jens Kuhle, Jonathan D. Rohrer, Charlotte E. Teunissen, John C. van Swieten^*

^*Corresponding author for this work

Imaging and Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

209 Citations (Scopus)

Abstract

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 (r_s= 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.

Original language	English
Pages (from-to)	623-636
Number of pages	14
Journal	Annals of Clinical and Translational Neurology
Volume	3
Issue number	8
Early online date	1 Jul 2016
DOIs	https://doi.org/10.1002/acn3.325
Publication status	Published - 1 Aug 2016

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Meeter, L. H., Dopper, E. G., Jiskoot, L. C., Sanchez-Valle, R., Graff, C., Benussi, L., Ghidoni, R., Pijnenburg, Y. A., Borroni, B., Galimberti, D., Laforce, R. J., Masellis, M., Vandenberghe, R., Ber, I. L., Otto, M., van Minkelen, R., Papma, J. M., Rombouts, S. A., Balasa, M., ... van Swieten, J. C. (2016). Neurofilament light chain: a biomarker for genetic frontotemporal dementia. Annals of Clinical and Translational Neurology, 3(8), 623-636. https://doi.org/10.1002/acn3.325

@article{3f0e5cc93d14482884b59fb7a92c93a2,

title = "Neurofilament light chain: a biomarker for genetic frontotemporal dementia",

abstract = "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.",

author = "Meeter, {Lieke H.} and Dopper, {Elise G.} and Jiskoot, {Lize C.} and Raquel Sanchez-Valle and Caroline Graff and Luisa Benussi and Roberta Ghidoni and Pijnenburg, {Yolande A.} and Barbara Borroni and Daniela Galimberti and Laforce, {Robert Jr} and Mario Masellis and Rik Vandenberghe and Ber, {Isabelle Le} and Markus Otto and {van Minkelen}, Rick and Papma, {Janne M.} and Rombouts, {Serge A.} and Mircea Balasa and Linn {\"O}ijerstedt and Vesna Jelic and Dick, {Katrina M.} and Cash, {David M.} and Harding, {Sophie R.} and {Jorge Cardoso}, M. and Sebastien Ourselin and Rossor, {Martin N.} and Alessandro Padovani and Elio Scarpini and Chiara Fenoglio and Tartaglia, {Maria C.} and Foudil Lamari and Christian Barro and Jens Kuhle and Rohrer, {Jonathan D.} and Teunissen, {Charlotte E.} and {van Swieten}, {John C.}",

year = "2016",

month = aug,

day = "1",

doi = "10.1002/acn3.325",

language = "English",

volume = "3",

pages = "623--636",

journal = "Annals of Clinical and Translational Neurology",

publisher = "John Wiley and Sons Ltd",

number = "8",

}

Meeter, LH, Dopper, EG, Jiskoot, LC, Sanchez-Valle, R, Graff, C, Benussi, L, Ghidoni, R, Pijnenburg, YA, Borroni, B, Galimberti, D, Laforce, RJ, Masellis, M, Vandenberghe, R, Ber, IL, Otto, M, van Minkelen, R, Papma, JM, Rombouts, SA, Balasa, M, Öijerstedt, L, Jelic, V, Dick, KM, Cash, DM, Harding, SR, Jorge Cardoso, M , Ourselin, S, Rossor, MN, Padovani, A, Scarpini, E, Fenoglio, C, Tartaglia, MC, Lamari, F, Barro, C, Kuhle, J, Rohrer, JD, Teunissen, CE & van Swieten, JC 2016, 'Neurofilament light chain: a biomarker for genetic frontotemporal dementia', Annals of Clinical and Translational Neurology, vol. 3, no. 8, pp. 623-636. https://doi.org/10.1002/acn3.325

TY - JOUR

T1 - Neurofilament light chain

T2 - 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 - Ber, Isabelle Le

AU - Otto, Markus

AU - van Minkelen, Rick

AU - Papma, Janne M.

AU - Rombouts, Serge A.

AU - Balasa, Mircea

AU - Öijerstedt, Linn

AU - Jelic, Vesna

AU - Dick, Katrina M.

AU - Cash, David M.

AU - Harding, Sophie R.

AU - Jorge Cardoso, M.

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 - 2016/8/1

Y1 - 2016/8/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85018393902&partnerID=8YFLogxK

U2 - 10.1002/acn3.325

DO - 10.1002/acn3.325

M3 - Article

AN - SCOPUS:85018393902

VL - 3

SP - 623

EP - 636

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

IS - 8

ER -

Neurofilament light chain: a biomarker for genetic frontotemporal dementia

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