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Inhibiting the Ca 2+ Influx Induced by Human CSF. / Drews, Anna; De, Suman; Flagmeier, Patrick; Wirthensohn, David C; Chen, Wei-Hsin; Whiten, Daniel R; Rodrigues, Margarida; Vincke, Cécile; Muyldermans, Serge; Paterson, Ross W; Slattery, Catherine F; Fox, Nick C; Schott, Jonathan M; Zetterberg, Henrik; Dobson, Christopher M; Gandhi, Sonia; Klenerman, David.

In: Cell Reports, Vol. 21, No. 11, 12.12.2017, p. 3310-3316.

Research output: Contribution to journalArticle

Harvard

Drews, A, De, S, Flagmeier, P, Wirthensohn, DC, Chen, W-H, Whiten, DR, Rodrigues, M, Vincke, C, Muyldermans, S, Paterson, RW, Slattery, CF, Fox, NC, Schott, JM, Zetterberg, H, Dobson, CM, Gandhi, S & Klenerman, D 2017, 'Inhibiting the Ca 2+ Influx Induced by Human CSF', Cell Reports, vol. 21, no. 11, pp. 3310-3316. https://doi.org/10.1016/j.celrep.2017.11.057

APA

Drews, A., De, S., Flagmeier, P., Wirthensohn, D. C., Chen, W-H., Whiten, D. R., ... Klenerman, D. (2017). Inhibiting the Ca 2+ Influx Induced by Human CSF. Cell Reports, 21(11), 3310-3316. https://doi.org/10.1016/j.celrep.2017.11.057

Vancouver

Drews A, De S, Flagmeier P, Wirthensohn DC, Chen W-H, Whiten DR et al. Inhibiting the Ca 2+ Influx Induced by Human CSF. Cell Reports. 2017 Dec 12;21(11):3310-3316. https://doi.org/10.1016/j.celrep.2017.11.057

Author

Drews, Anna ; De, Suman ; Flagmeier, Patrick ; Wirthensohn, David C ; Chen, Wei-Hsin ; Whiten, Daniel R ; Rodrigues, Margarida ; Vincke, Cécile ; Muyldermans, Serge ; Paterson, Ross W ; Slattery, Catherine F ; Fox, Nick C ; Schott, Jonathan M ; Zetterberg, Henrik ; Dobson, Christopher M ; Gandhi, Sonia ; Klenerman, David. / Inhibiting the Ca 2+ Influx Induced by Human CSF. In: Cell Reports. 2017 ; Vol. 21, No. 11. pp. 3310-3316.

BibTeX

@article{322d2cc8461c4227bf0f4d835a5ff4a2,
title = "Inhibiting the Ca 2+ Influx Induced by Human CSF",
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 Ca 2+ 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 Ca 2+ 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. Drews et al. develop and implement sensitive in vitro assays to quantitatively measure the Ca 2+ influx caused by human cerebrospinal fluid. If a given chaperone, antibody, or nanobody is effective in reducing Ca 2+ influx, the authors determine what concentration is needed to prevent Ca 2+ influx.",
keywords = "Alzheimer's disease, antibodies, beta amyloid, calcium influx, cerebrospinal fluid, clusterin, fluorescence measurements, neurodegenerative conditions, oligomers, single molecule imaging",
author = "Anna Drews and Suman De and Patrick Flagmeier and Wirthensohn, {David C} and Wei-Hsin Chen and Whiten, {Daniel R} and Margarida Rodrigues and C{\'e}cile Vincke and Serge Muyldermans and Paterson, {Ross W} and Slattery, {Catherine F} and Fox, {Nick C} and Schott, {Jonathan M} and Henrik Zetterberg and Dobson, {Christopher M} and Sonia Gandhi and David Klenerman",
note = "Copyright {\circledC} 2017 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = "12",
day = "12",
doi = "10.1016/j.celrep.2017.11.057",
language = "English",
volume = "21",
pages = "3310--3316",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",

}

RIS

TY - JOUR

T1 - Inhibiting the Ca 2+ Influx Induced by Human CSF

AU - Drews, Anna

AU - De, Suman

AU - Flagmeier, Patrick

AU - Wirthensohn, David C

AU - Chen, Wei-Hsin

AU - Whiten, Daniel R

AU - Rodrigues, Margarida

AU - Vincke, Cécile

AU - Muyldermans, Serge

AU - Paterson, Ross W

AU - Slattery, Catherine F

AU - Fox, Nick C

AU - Schott, Jonathan M

AU - Zetterberg, Henrik

AU - Dobson, Christopher M

AU - Gandhi, Sonia

AU - Klenerman, David

N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2017/12/12

Y1 - 2017/12/12

N2 - 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 Ca 2+ 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 Ca 2+ 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. Drews et al. develop and implement sensitive in vitro assays to quantitatively measure the Ca 2+ influx caused by human cerebrospinal fluid. If a given chaperone, antibody, or nanobody is effective in reducing Ca 2+ influx, the authors determine what concentration is needed to prevent Ca 2+ influx.

AB - 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 Ca 2+ 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 Ca 2+ 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. Drews et al. develop and implement sensitive in vitro assays to quantitatively measure the Ca 2+ influx caused by human cerebrospinal fluid. If a given chaperone, antibody, or nanobody is effective in reducing Ca 2+ influx, the authors determine what concentration is needed to prevent Ca 2+ influx.

KW - Alzheimer's disease

KW - antibodies

KW - beta amyloid

KW - calcium influx

KW - cerebrospinal fluid

KW - clusterin

KW - fluorescence measurements

KW - neurodegenerative conditions

KW - oligomers

KW - single molecule imaging

UR - http://www.scopus.com/inward/record.url?scp=85037849582&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.11.057

DO - 10.1016/j.celrep.2017.11.057

M3 - Article

C2 - 29241555

VL - 21

SP - 3310

EP - 3316

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 11

ER -

ID: 36663364