Neurofilament light chain: a biomarker for genetic frontotemporal dementia

Medientyp: E-Artikel
Titel: Neurofilament light chain: a biomarker for genetic frontotemporal dementia
Beteiligte: Meeter, Lieke H.; Dopper, Elise G.; Jiskoot, Lize C.; Sanchez‐Valle, Raquel; Graff, Caroline; Benussi, Luisa; Ghidoni, Roberta; Pijnenburg, Yolande A.; Borroni, Barbara; Galimberti, Daniela; Laforce, Robert Jr; Masellis, Mario; Vandenberghe, Rik; Ber, Isabelle Le; Otto, Markus; van Minkelen, Rick; Papma, Janne M.; Rombouts, Serge A.; Balasa, Mircea; Öijerstedt, Linn; Jelic, Vesna; Dick, Katrina M.; Cash, David M.; Harding, Sophie R.; [...]
Erschienen: Wiley, 2016
Erschienen in: Annals of Clinical and Translational Neurology
Sprache: Englisch
DOI: 10.1002/acn3.325
ISSN: 2328-9503
Schlagwörter: Neurology (clinical) ; General Neuroscience
Entstehung:
Anmerkungen:
Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To evaluate cerebrospinal fluid (<jats:styled-content style="fixed-case">CSF</jats:styled-content>) and serum neurofilament light chain (NfL) levels in genetic frontotemporal dementia (<jats:styled-content style="fixed-case">FTD</jats:styled-content>) 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this multicenter case–control study, we investigated <jats:styled-content style="fixed-case">CSF</jats:styled-content> NfL in 174 subjects (48 controls, 40 presymptomatic carriers and 86 patients with <jats:italic>microtubule‐associated protein tau</jats:italic> (<jats:italic><jats:styled-content style="fixed-case">MAPT</jats:styled-content></jats:italic>), <jats:italic>progranulin</jats:italic> (<jats:italic><jats:styled-content style="fixed-case">GRN</jats:styled-content></jats:italic>), and <jats:italic>chromosome 9 open reading frame 72</jats:italic> (<jats:italic>C9orf72</jats:italic>) mutations), and serum NfL in 118 subjects (39 controls, 44 presymptomatic carriers, 35 patients). In 55 subjects both <jats:styled-content style="fixed-case">CSF</jats:styled-content> and serum was determined. In two subjects <jats:styled-content style="fixed-case">CSF</jats:styled-content> was available before and after symptom onset (converters). Additionally, NfL levels were correlated with clinical parameters, survival, and regional brain atrophy.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:styled-content style="fixed-case">CSF</jats:styled-content> 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, <jats:italic>P</jats:italic> < 0.001), resulting in a good diagnostic performance to discriminate both groups. Serum NfL correlated highly with <jats:styled-content style="fixed-case">CSF</jats:styled-content> NfL (<jats:italic>r</jats:italic><jats:sub><jats:italic>s</jats:italic> </jats:sub>= 0.87, <jats:italic>P</jats:italic> < 0.001) and was similarly elevated in patients. Longitudinal samples in the converters showed a three‐ to fourfold increase in <jats:styled-content style="fixed-case">CSF</jats:styled-content> NfL after disease onset. Additionally, NfL levels in patients correlated with disease severity, brain atrophy, annualized brain atrophy rate and survival.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>NfL in both serum and <jats:styled-content style="fixed-case">CSF</jats:styled-content> has the potential to serve as a biomarker for clinical disease onset and has a prognostic value in genetic <jats:styled-content style="fixed-case">FTD</jats:styled-content>.</jats:p></jats:sec>
Zugangsstatus: Freier Zugang

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: