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A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid

INTRODUCTION: Amyloid β-protein oligomers play a key role in Alzheimer’s disease (AD), but well-validated assays that routinely detect them in cerebrospinal fluid (CSF) are just emerging. We sought to confirm and extend a recent study using the Singulex Erenna platform that reported increased mean C...

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Autores principales: Yang, Ting, O’Malley, Tiernan T, Kanmert, Daniel, Jerecic, Jasna, Zieske, Lynn R, Zetterberg, Henrik, Hyman, Bradley T, Walsh, Dominic M, Selkoe, Dennis J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369838/
https://www.ncbi.nlm.nih.gov/pubmed/25802556
http://dx.doi.org/10.1186/s13195-015-0100-y
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author Yang, Ting
O’Malley, Tiernan T
Kanmert, Daniel
Jerecic, Jasna
Zieske, Lynn R
Zetterberg, Henrik
Hyman, Bradley T
Walsh, Dominic M
Selkoe, Dennis J
author_facet Yang, Ting
O’Malley, Tiernan T
Kanmert, Daniel
Jerecic, Jasna
Zieske, Lynn R
Zetterberg, Henrik
Hyman, Bradley T
Walsh, Dominic M
Selkoe, Dennis J
author_sort Yang, Ting
collection PubMed
description INTRODUCTION: Amyloid β-protein oligomers play a key role in Alzheimer’s disease (AD), but well-validated assays that routinely detect them in cerebrospinal fluid (CSF) are just emerging. We sought to confirm and extend a recent study using the Singulex Erenna platform that reported increased mean CSF oligomer levels in AD. METHODS: We tested four antibody pairs and chose one pair that was particularly sensitive, using 1C22, our new oligomer-selective monoclonal antibody, for capture. We applied this new assay to extracts of human brain and CSF. RESULTS: A combination of 1C22 for capture and 3D6 for detection yielded an Erenna immunoassay with a lower limit of quantification of approximately 0.15 pg/ml that was highly selective for oligomers over monomers and detected a wide size-range of oligomers. Most CSFs we tested had detectable oligomer levels but with a large overlap between AD and controls and a trend for higher mean levels in mild cognitive impairment (MCI) than controls. CONCLUSION: Aβ oligomers are detectable in most human CSFs, but AD and controls overlap. MCI CSFs may have a modest elevation in mean value by this assay. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-015-0100-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-43698382015-03-24 A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid Yang, Ting O’Malley, Tiernan T Kanmert, Daniel Jerecic, Jasna Zieske, Lynn R Zetterberg, Henrik Hyman, Bradley T Walsh, Dominic M Selkoe, Dennis J Alzheimers Res Ther Research INTRODUCTION: Amyloid β-protein oligomers play a key role in Alzheimer’s disease (AD), but well-validated assays that routinely detect them in cerebrospinal fluid (CSF) are just emerging. We sought to confirm and extend a recent study using the Singulex Erenna platform that reported increased mean CSF oligomer levels in AD. METHODS: We tested four antibody pairs and chose one pair that was particularly sensitive, using 1C22, our new oligomer-selective monoclonal antibody, for capture. We applied this new assay to extracts of human brain and CSF. RESULTS: A combination of 1C22 for capture and 3D6 for detection yielded an Erenna immunoassay with a lower limit of quantification of approximately 0.15 pg/ml that was highly selective for oligomers over monomers and detected a wide size-range of oligomers. Most CSFs we tested had detectable oligomer levels but with a large overlap between AD and controls and a trend for higher mean levels in mild cognitive impairment (MCI) than controls. CONCLUSION: Aβ oligomers are detectable in most human CSFs, but AD and controls overlap. MCI CSFs may have a modest elevation in mean value by this assay. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-015-0100-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-22 /pmc/articles/PMC4369838/ /pubmed/25802556 http://dx.doi.org/10.1186/s13195-015-0100-y Text en © Yang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Yang, Ting
O’Malley, Tiernan T
Kanmert, Daniel
Jerecic, Jasna
Zieske, Lynn R
Zetterberg, Henrik
Hyman, Bradley T
Walsh, Dominic M
Selkoe, Dennis J
A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid
title A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid
title_full A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid
title_fullStr A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid
title_full_unstemmed A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid
title_short A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid
title_sort highly sensitive novel immunoassay specifically detects low levels of soluble aβ oligomers in human cerebrospinal fluid
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369838/
https://www.ncbi.nlm.nih.gov/pubmed/25802556
http://dx.doi.org/10.1186/s13195-015-0100-y
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