Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia
Open Access
- 9 April 2020
- journal article
- research article
- Published by BMJ in Journal of Neurology, Neurosurgery & Psychiatry
- Vol. 91 (6), 612-621
- https://doi.org/10.1136/jnnp-2019-322493
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), pDiscussion We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.Funding Information
- Deutsche Forschungsgemeinschaft
- Horizon 2020 Framework Programme (779357)
- schorling foundation
- NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH)
- Stockholms Läns Landsting
- Munich Cluster for Systems Neurology (EXC 2145 SyNergy 390857198)
- Swedish Demensfonden
- Swedish FTD Initiative
- The Bluefield Project to Cure Frontotemporal Dementia
- Stichting Dioraphte (1402 1300)
- swedish alzheimer foundation
- Stiftelsen för Gamla Tjänarinnor
- Vetenskapsrådet (2015-02926, 2018-02754, 529-2014-7504)
- Hjärnfonden
- MRC UK (MR/M023664/1)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (733050103, 733050813)
- Alzheimer Nederland (733050103, 733050813)
- Stratneuro
- European Joint Programme - Neurodegenerative Disease Research (733051024, 733051042)
- Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie
- Karolinska Institutet Doctoral Funding
- fundacio marato de TV3 (20143810)
- MRC Clinician Scientist Fellowship (MR/M008525/1)
- Wellcome Trust (103838)
- Alzheimer's Society (As-PhD-2015-005)
This publication has 41 references indexed in Scilit:
- Identification of longitudinally dynamic biomarkers in Alzheimer’s disease cerebrospinal fluid by targeted proteomicsMolecular Neurodegeneration, 2014
- Synaptic dysfunction in progranulin-deficient miceNeurobiology of Disease, 2012
- Proteomic Changes in Cerebrospinal Fluid of Presymptomatic and Affected Persons Carrying Familial Alzheimer Disease MutationsArchives of Neurology, 2012
- Progranulin Deficiency Decreases Gross Neural Connectivity But Enhances Transmission at Individual SynapsesJournal of Neuroscience, 2011
- Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementiaBrain, 2011
- Classification of primary progressive aphasia and its variantsNeurology, 2011
- Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneuronsNature Neuroscience, 2010
- Neuronal pentraxin receptor in cerebrospinal fluid as a potential biomarker for neurodegenerative diseasesBrain Research, 2009
- Neuronal pentraxin II is highly upregulated in Parkinson’s disease and a novel component of Lewy bodiesActa Neuropathologica, 2007
- Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairmentAnnals of Neurology, 1991