Suchergebnisse

Objective To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimers disease-related amyloid beta (A beta) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. Methods The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinsons disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimers disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPP alpha) and beta (sAPP beta), A beta species (A beta 38, A beta 40 and A beta 42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). Results Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, A beta 40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, A beta 40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. Conclusions The combination of the CSF biomarkers T-tau, A beta 40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH. ; Funding Agencies|Swedish Research CouncilSwedish Research Council [2017-00915]; Swedish government; ALF [2017-04961, ALFGBG-720931, ALFGBG-720121, ALFGBG715986]; Swedish Alzheimer Foundation [F-742881]; Hjarnfonden, Sweden [FO2017-0243]; Kuopio University Hospital; Goteborg Foundation for Neurological Research

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 ...