Neurofilament light chain: a biomarker for genetic frontotemporal dementia.
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.



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.



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.



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.
Alzheimer Center Rotterdam and Department of Neurology Erasmus Medical Center PO Box 2040, 3000 CA Rotterdam The Netherlands.
Lieke H
LH
Meeter
Alzheimer Center Rotterdam and Department of Neurology Erasmus Medical Center PO Box 2040, 3000 CA Rotterdam The Netherlands.
Elise G
EG
Dopper
Alzheimer Center Rotterdam and Department of Neurology Erasmus Medical Center PO Box 2040, 3000 CA Rotterdam The Netherlands.
Lize C
LC
Jiskoot
Alzheimer's Disease and Other Cognitive Disorders Unit Department of Neurology Hospital Clínic Institut d'Investigació Biomèdica August Pi i Sunyer Villarroel, 170 Barcelona 08036 Spain.
Raquel
R
Sanchez-Valle
Division of Neurogeriatrics Department NVS, Karolinska Institutet Center for Alzheimer Research Huddinge 141 57 Sweden; Department of Geriatric Medicine Karolinska University Hospital- Huddinge Stockholm 141 86 Sweden.
Caroline
C
Graff
Molecular Markers Laboratory IRCCS Centro San Giovanni di Dio Fatebenefratelli via Pilastroni 4 Brescia 25125 Italy.
Luisa
L
Benussi
Molecular Markers Laboratory IRCCS Centro San Giovanni di Dio Fatebenefratelli via Pilastroni 4 Brescia 25125 Italy.
Roberta
R
Ghidoni
Alzheimer Center and Department of Neurology Neuroscience Campus Amsterdam VU University Medical Center PO Box 7057, 1007 MB Amsterdam The Netherlands.
Yolande A
YA
Pijnenburg
Neurology Unit Department of Clinical and Experimental Sciences Centre for Neurodegenerative Diseases University of Brescia Brescia Italy.
Barbara
B
Borroni
University of Milan Fondazione Ca' Granda IRCSS Ospedale Policlinico Milan Italy.
Daniela
D
Galimberti
Département des Sciences Neurologiques Clinique Interdisciplinaire de Mémoire (CIME) CHU de Québec Université Laval Québec Canada.
Robert Jr
RJ
Laforce
Division of Neurology Department of Medicine Sunnybrook Health Sciences Centre University of Toronto Toronto Canada; Hurvitz Brain Sciences Research Program Sunnybrook Research Institute Toronto Canada.
Mario
M
Masellis
Neurology University Hospitals Leuven Herestraat 49 Leuven Belgium; Laboratory for Cognitive Neurology Department of Neurosciences KU Leuven Leuven Belgium.
Rik
R
Vandenberghe
Institut du Cerveau et de la Moelle épinière (ICM) Inserm U1127 CNRS UMR 7225 Sorbonne Universités Université Pierre et Marie Curie Univ Paris 06U PMC-P6 UMR S 1127 - Hôpital Pitié-Salpêtrière Paris France; Centre de Référence des Démences Rares AP-HP Hôpital de la Pitié-Salpêtrière Paris France; Département des maladies du système nerveux AP-HP Hôpital de la Pitié-Salpêtrière Paris France.
Isabelle Le
IL
Ber
Department of Neurology Ulm University Ulm Germany; German FTLD consortium Department of Neurology University of Ulm Ulm Germany.
Markus
M
Otto
Department of Clinical Genetics Erasmus Medical Center PO Box 2040, 3000 CA Rotterdam The Netherlands.
Rick
R
van Minkelen
Alzheimer Center Rotterdam and Department of Neurology Erasmus Medical Center PO Box 2040, 3000 CA Rotterdam The Netherlands.
Janne M
JM
Papma
Institute of Psychology Leiden University Leiden The Netherlands; Department of Radiology Leiden University Medical Center Leiden The Netherlands.
Serge A
SA
Rombouts
Alzheimer's Disease and Other Cognitive Disorders Unit Department of Neurology Hospital Clínic Institut d'Investigació Biomèdica August Pi i Sunyer Villarroel, 170 Barcelona 08036 Spain.
Mircea
M
Balasa
Division of Neurogeriatrics Department NVS, Karolinska Institutet Center for Alzheimer Research Huddinge 141 57 Sweden; Department of Geriatric Medicine Karolinska University Hospital- Huddinge Stockholm 141 86 Sweden.
Linn
L
Öijerstedt
Department of Geriatric Medicine Karolinska University Hospital- Huddinge Stockholm 141 86 Sweden; Division of clinical geriatrics Deptartment NVS Karolinska Institutet Center for Alzheimer Research Huddinge 141 57 Sweden.
Vesna
V
Jelic
Dementia Research Centre Department of Neurodegenerative Disease Institute of Neurology University College London WC1N 3BG London United Kingdom.
Katrina M
KM
Dick
Division of clinical geriatrics Department NVS Karolinska Institutet Center for Alzheimer Research Huddinge 141 57 Sweden; Translational Imaging Group Centre for Medical Image Computing University College London NW1 2HE London United Kingdom.
David M
DM
Cash
Dementia Research Centre Department of Neurodegenerative Disease Institute of Neurology University College London WC1N 3BG London United Kingdom.
Sophie R
SR
Harding
Dementia Research Centre Department of Neurodegenerative Disesase Institute of Neurology University College London WC1N 3BG London United Kingdom; Translational Imaging Group Centre for Medical Image Computing University College London NW1 2HE London United Kingdom.
M
M
Jorge Cardoso
Translational Imaging Group Centre for Medical Image Computing University College London NW1 2HE London United Kingdom.
Sebastien
S
Ourselin
Dementia Research Centre Department of Neurodegenerative Disease Institute of Neurology University College London WC1N 3BG London United Kingdom.
Martin N
MN
Rossor
Neurology Unit Department of Clinical and Experimental Sciences Centre for Neurodegenerative Diseases University of Brescia Brescia Italy.
Alessandro
A
Padovani
University of Milan Fondazione Ca' Granda IRCSS Ospedale Policlinico Milan Italy.
Elio
E
Scarpini
University of Milan Fondazione Ca' Granda IRCSS Ospedale Policlinico Milan Italy.
Chiara
C
Fenoglio
Laboratoire de Biochimie AP-HP Hopital Pitié-Salpétrière Paris France.
Maria C
MC
Tartaglia
Tanz Center for Research in Neurodegenerative Diseases University of Toronoto Toronoto Canada.
Foudil
F
Lamari
Neurology Departments of Medicine Biomedicine and Clinical Research University Hospital Basel Basel Switzerland.
Christian
C
Barro
Neurology Departments of Medicine Biomedicine and Clinical Research University Hospital Basel Basel Switzerland.
Jens
J
Kuhle
Dementia Research Centre Department of Neurodegenerative Disease Institute of Neurology University College London WC1N 3BG London United Kingdom.
Jonathan D
JD
Rohrer
Neurochemistry Lab and Biobank Department of Clinical Chemistry Neuroscience Campus VU University Medical Center PO Box 7057, 1007 MB Amsterdam The Netherlands.
Charlotte E
CE
Teunissen
Alzheimer Center Rotterdam and Department of Neurology Erasmus Medical Center PO Box 2040, 3000 CA Rotterdam The Netherlands; Department of Clinical Genetics VU University Medical Center PO Box 7057, 1007 MB Amsterdam The Netherlands.
John C
JC
van Swieten