TY - JOUR
T1 - Neuronal pentraxin 2
T2 - A synapse-derived CSF biomarker in genetic frontotemporal dementia
AU - Van Der Ende, Emma L.
AU - Xiao, Meifang
AU - Xu, Desheng
AU - Poos, Jackie M.
AU - Panman, Jessica L.
AU - Panman, Jessica L.
AU - Jiskoot, Lize C.
AU - Jiskoot, Lize C.
AU - Meeter, Lieke H.
AU - Dopper, Elise G.P.
AU - Papma, Janne M.
AU - Heller, Carolin
AU - Convery, Rhian
AU - Moore, Katrina
AU - Bocchetta, Martina
AU - Neason, Mollie
AU - Peakman, Georgia
AU - Cash, David M.
AU - Teunissen, Charlotte E.
AU - Graff, Caroline
AU - Graff, Caroline
AU - Synofzik, Matthis
AU - Synofzik, Matthis
AU - Moreno, Fermin
AU - Finger, Elizabeth
AU - Sánchez-Valle, Raquel
AU - Vandenberghe, Rik
AU - Laforce, Robert
AU - Masellis, Mario
AU - Tartaglia, Maria Carmela
AU - Rowe, James B.
AU - Butler, Christopher R.
AU - Ducharme, Simon
AU - Gerhard, Alex
AU - Gerhard, Alex
AU - Danek, Adrian
AU - Levin, Johannes
AU - Levin, Johannes
AU - Levin, Johannes
AU - Pijnenburg, Yolande A.L.
AU - Otto, Markus
AU - Borroni, Barbara
AU - Tagliavini, Fabrizio
AU - De Mendonca, Alexandre
AU - Santana, Isabel
AU - Galimberti, Daniela
AU - Galimberti, Daniela
AU - Seelaar, Harro
AU - Rohrer, Jonathan D.
AU - Worley, Paul F.
AU - Worley, Paul F.
AU - Van Swieten, John C.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Introduction Synapse dysfunction is emerging as an early pathological event in frontotemporal dementia (FTD), however biomarkers are lacking. We aimed to investigate the value of cerebrospinal fluid (CSF) neuronal pentraxins (NPTXs), a family of proteins involved in homeostatic synapse plasticity, as novel biomarkers in genetic FTD. Methods We included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN, C9orf72 or MAPT, and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses. Results Symptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301-872)) than presymptomatic carriers (1003 pg/mL (624-1358), p<0.001) and non-carriers (990 pg/mL (597-1373), p<0.001) (corrected for age). Similar results were found for NPTX1 and NPTXR. Among mutation carriers, NPTX2 concentration correlated with several clinical disease severity measures, NfL and grey matter volume of the frontal, temporal and parietal lobes, insula and whole brain. NPTX2 predicted subsequent decline in phonemic verbal fluency and Clinical Dementia Rating scale plus FTD modules. In longitudinal CSF samples, available in 13 subjects, NPTX2 decreased around symptom onset and in the symptomatic stage. Discussion We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.
AB - Introduction Synapse dysfunction is emerging as an early pathological event in frontotemporal dementia (FTD), however biomarkers are lacking. We aimed to investigate the value of cerebrospinal fluid (CSF) neuronal pentraxins (NPTXs), a family of proteins involved in homeostatic synapse plasticity, as novel biomarkers in genetic FTD. Methods We included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN, C9orf72 or MAPT, and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses. Results Symptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301-872)) than presymptomatic carriers (1003 pg/mL (624-1358), p<0.001) and non-carriers (990 pg/mL (597-1373), p<0.001) (corrected for age). Similar results were found for NPTX1 and NPTXR. Among mutation carriers, NPTX2 concentration correlated with several clinical disease severity measures, NfL and grey matter volume of the frontal, temporal and parietal lobes, insula and whole brain. NPTX2 predicted subsequent decline in phonemic verbal fluency and Clinical Dementia Rating scale plus FTD modules. In longitudinal CSF samples, available in 13 subjects, NPTX2 decreased around symptom onset and in the symptomatic stage. Discussion We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.
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U2 - 10.1136/jnnp-2019-322493
DO - 10.1136/jnnp-2019-322493
M3 - Article
C2 - 32273328
AN - SCOPUS:85083204915
SN - 0022-3050
VL - 91
SP - 612
EP - 621
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 6
ER -