Drews, A., De, S. orcid.org/0000-0003-1675-0773, Flagmeier, P. et al. (14 more authors) (2017) Inhibiting the Ca 2+ influx induced by human CSF. Cell Reports, 21 (11). pp. 3310-3316. ISSN 2211-1247
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | neurodegenerative conditions; Alzheimer’s disease; cerebrospinal fluid; beta amyloid; oligomers; clusterin; antibodies; single molecule imaging; fluorescence measurements; calcium influx |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 May 2020 15:25 |
Last Modified: | 01 May 2020 15:26 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.celrep.2017.11.057 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:160189 |