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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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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. |
format | Online Article Text |
id | pubmed-4369838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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