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Inhibiting the Ca2+ Influx Induced by Human CSF

Drews, A; De, S; Flagmeier, P; Wirthensohn, DC; Chen, W-H; Whiten, DR; Vincke, C; ... Klenerman, D; + view all (2017) Inhibiting the Ca2+ Influx Induced by Human CSF. Cell Reports , 21 (11) pp. 3310-3316. 10.1016/j.celrep.2017.11.057. Green open access

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Abstract

One potential therapeutic strategy for Alzheimer’s disease (AD) is to use antibodies that bind to small soluble protein aggregates to reduce their toxic effects. However, these therapies are rarely tested in human CSF before clinical trials because of the lack of sensitive methods that enable the measurement of aggregate-induced toxicity at low concentrations. We have developed highly sensitive single vesicle and single-cell-based assays that detect the Ca2+ influx caused by the CSF of individuals affected with AD and healthy controls, and we have found comparable effects for both types of samples. We also show that an extracellular chaperone clusterin; a nanobody specific to the amyloid-β peptide (Aβ); and bapineuzumab, a humanized monoclonal antibody raised against Aβ, could all reduce the Ca2+ influx caused by synthetic Aβ oligomers but are less effective in CSF. These assays could be used to characterize potential therapeutic agents in CSF before clinical trials.

Type: Article
Title: Inhibiting the Ca2+ Influx Induced by Human CSF
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2017.11.057
Publisher version: http://doi.org/10.1016/j.celrep.2017.11.057
Language: English
Additional information: Copyright © 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: neurodegenerative conditionsAlzheimer’s disease, cerebrospinal fluidbeta amyloidoligomers, clusterin, antibodiessingle molecule imaging, fluorescence measurements, calcium influx
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10041163
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