RT Journal Article
SR Electronic
T1 Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 612
OP 621
DO 10.1136/jnnp-2019-322493
VO 91
IS 6
A1 Emma L van der Ende
A1 Meifang Xiao
A1 Desheng Xu
A1 Jackie M Poos
A1 Jessica L Panman
A1 Lize C Jiskoot
A1 Lieke H Meeter
A1 Elise GP Dopper
A1 Janne M Papma
A1 Carolin Heller
A1 Rhian Convery
A1 Katrina Moore
A1 Martina Bocchetta
A1 Mollie Neason
A1 Georgia Peakman
A1 David M Cash
A1 Charlotte E Teunissen
A1 Caroline Graff
A1 Matthis Synofzik
A1 Fermin Moreno
A1 Elizabeth Finger
A1 Raquel Sánchez-Valle
A1 Rik Vandenberghe
A1 Robert Laforce Jr
A1 Mario Masellis
A1 Maria Carmela Tartaglia
A1 James B Rowe
A1 Christopher R Butler
A1 Simon Ducharme
A1 Alex Gerhard
A1 Adrian Danek
A1 Johannes Levin
A1 Yolande AL Pijnenburg
A1 Markus Otto
A1 Barbara Borroni
A1 Fabrizio Tagliavini
A1 Alexandre de Mendonca
A1 Isabel Santana
A1 Daniela Galimberti
A1 Harro Seelaar
A1 Jonathan D Rohrer
A1 Paul F Worley
A1 John C van Swieten
A1 ,
YR 2020
UL http://jnnp.bmj.com/content/91/6/612.abstract
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.