Suchergebnisse

Altres ajuts: C. E. Teunissen PhD received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer's Drug Discovery Foundation, Alzheimer Netherlands. M. Otto MD PhD received funding from the EU, German ministry of science and technology (KNDD/FTLD) the Baden-Wuertemberg Foundation. Sebastiaan Engelborghs MD, PhD received funding from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant number 115372); the University Research Fund of the University of Antwerp; the Flemish Impulse Financing of Networks for Dementia Research (VIND); and Flanders Innovation & Entrepreneurship (VLAIO). Sanna-Kaisa Herukka MD, PhD received funding from Finnish Medical Foundation and Finnish Medical Society Duodecim. Sylvain Lehmann MD, PhD has received support from "France Alzheimer", the National French Alzheimer effort ("Plan Alzheimer"). Piotr Lewczuk MD, PhD has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement number 115372, resources of which are composed of financia contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. Hayrettin Tumani MD received research support from Hertie-Stiftung, BMBF, University of Ulm and Landesstiftung BW. Martin R. Turner MBBS, PhD is supported by the Medical Research Council & Motor Neurone Disease Association Lady Edith Wolfson Senior Clinical Fellowship (MR/K01014X/1). MM Verbeek PhD received grants from Alzheimer Nederland (number 14502) and the CAVIA project, which has been made possible by ZonMW (number 733050202). The CAVIA project is part of 'Memorabel', the research and innovation programme for dementia, as part of the Dutch national 'Deltaplan for Dementia': zonmw.nl/dementiaresearch. The CAVIA project is a consortium of Radboudumc, LUMC, Erasmus MC, VUmc, ADX Neurosciences, Philips Healthcare, Stony Brook University and Massachusetts General Hospital. Jens Wiltfang is ...

© 2020 – IOS Press and the authors. ; [Background]: Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown. [Objective]: We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes. [Methods]: We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677). [Results]: We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T–N–, A+T+N–, A+T–N+, and A+T+N+) from no AD pathology (A–T–N–) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts. [Conclusions]: Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo. ; This research was conducted as part of the EMIF-AD project which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in-kind contribution. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the 5th framework program (contract # 37670). The Leuven cohort was funded by the Stichting voor Alzheimer Onderzoek (grant numbers #11020, #13007 and #15005). The Lausanne cohort study was supported by a grant from the Swiss National Research Foundation to JP (SNF 320030_141179). RV is a senior clinical investigator of the Flemish Research Foundation (FWO). JS is currently an employee of UCB, Braine-l'Alleud, Belgium. The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). We acknowledge the contribution of the personnel of the Genomic Service Facility at the VIB-U Antwerp Center for Molecular Neurology. The research at VIB-CMN is funded in part by the University of Antwerp Research Fund. FB is supported by the NIHR biomedical research centre at UCLH. RD is supported by Health Data Research UK, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London, Maudsley NHS Foundation Trust, King's College London and the NIHR University College London Hospitals Biomedical Research Centre. LS is funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215). Also support was received from the NIHR Biomedical Research Centre at Oxford Health NHS Foundation Trust.