Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia. Issue 6 (9th April 2020)

• Record Type: Journal Article
• Authors: van der Ende, Emma L; Xiao, Meifang; Xu, Desheng; Poos, Jackie M; Panman, Jessica L; Jiskoot, Lize C; Meeter, Lieke H; Dopper, Elise GP; Papma, Janne M; Heller, Carolin; Convery, Rhian; Moore, Katrina; Bocchetta, Martina; Neason, Mollie; Peakman, Georgia; Cash, David M; Teunissen, Charlotte E; Graff, Caroline; Synofzik, Matthis; Moreno, Fermin; Finger, Elizabeth; Sánchez-Valle, Raquel; Vandenberghe, Rik; Laforce Jr, Robert; Masellis, Mario; Tartaglia, Maria Carmela; Rowe, James B; Butler, Christopher R; Ducharme, Simon; Gerhard, Alex; Danek, Adrian; Levin, Johannes; Pijnenburg, Yolande AL; Otto, Markus; Borroni, Barbara; Tagliavini, Fabrizio; de Mendonca, Alexandre; Santana, Isabel; Galimberti, Daniela; Seelaar, Harro; Rohrer, Jonathan D; Worley, Paul F; van Swieten, John C;
• Other Names: author non-byline.; Rossor Martin N author non-byline.; Warren Jason D author non-byline.; Fox Nick C author non-byline.; Guerreiro Rita author non-byline.; Bras Jose author non-byline.; Nicholas Jennifer author non-byline.; Mead Simon author non-byline.; Jiskoot Lize author non-byline.; Meeter Lieke author non-byline.; Panman Jessica author non-byline.; Barandiaran Myriam author non-byline.; Indakoetxea Begoña author non-byline.; Gabilondo Alazne author non-byline.; Tainta Mikel author non-byline.; Arriba Maria de author non-byline.; Gorostidi Ana author non-byline.; Zulaica Miren author non-byline.; Villanua Jorge author non-byline.; Borrego-Ecija Sergi author non-byline.; Olives Jaume author non-byline.; Lladó Albert author non-byline.; Balasa Mircea author non-byline.; Antonell Anna author non-byline.; Bargallo Nuria author non-byline.; Premi Enrico author non-byline.; Cosseddu Maura author non-byline.; Gazzina Stefano author non-byline.; Padovani Alessandro author non-byline.; Gasparotti Roberto author non-byline.; Archetti Silvana author non-byline.; Black Sandra author non-byline.; Mitchell Sara author non-byline.; Rogaeva Ekaterina author non-byline.; Freedman Morris author non-byline.; Keren Ron author non-byline.; Tang-Wai David author non-byline.; Öijerstedt Linn author non-byline.; Andersson Christin author non-byline.; Jelic Vesna author non-byline.; Thonberg Hakan author non-byline.; Arighi Andrea author non-byline.; Fenoglio Chiara author non-byline.; Scarpini Elio author non-byline.; Fumagalli Giorgio author non-byline.; Cope Thomas author non-byline.; Timberlake Carolyn author non-byline.; Rittman Timothy author non-byline.; Shoesmith Christen author non-byline.; Bartha Robart author non-byline.; Rademakers Rosa author non-byline.; Wilke Carlo author non-byline.; Karnarth Hans-Otto author non-byline.; Bender Benjamin author non-byline.; Bruffaerts Rose author non-byline.; Vandamme Philip author non-byline.; Vandenbulcke Mathieu author non-byline.; Ferreira Catarina B author non-byline.; Miltenberger Gabriel author non-byline.; Maruta Carolina author non-byline.; Verdelho Ana author non-byline.; Afonso Sónia author non-byline.; Taipa Ricardo author non-byline.; Caroppo Paola author non-byline.; Fede Giuseppe Di author non-byline.; Giaccone Giorgio author non-byline.; Prioni Sara author non-byline.; Redaelli Veronica author non-byline.; Rossi Giacomina author non-byline.; Tiraboschi Pietro author non-byline.; Duro Diana author non-byline.; Almeida Maria Rosario author non-byline.; Castelo-Branco Miguel author non-byline.; Leitão Maria João author non-byline.; Tabuas-Pereira Miguel author non-byline.; Santiago Beatriz author non-byline.; Gauthier Serge author non-byline.; Rosa-Neto Pedro author non-byline.; Veldsman Michele author non-byline.; Flanagan Toby author non-byline.; Prix Catharina author non-byline.; Hoegen Tobias author non-byline.; Wlasich Elisabeth author non-byline.; Loosli Sandra author non-byline.; Schonecker Sonja author non-byline.; Semler Elisa author non-byline.; Anderl-Straub Sarah author non-byline.; Benussi Luisa author non-byline.; Binetti Giuliano author non-byline.; Ghidoni Roberta author non-byline.; Pievani Michela author non-byline.; Lombardi Gemma author non-byline.; Nacmias Benedetta author non-byline.; Ferrari Camilla author non-byline.; Bessi Valentina author non-byline.;
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 91:Issue 6(2020)
• Page Start: 612
• Page End: 621
• Publication Date: 2020-04-09
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2019-322493
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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.