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

Ting Yang, Tiernan T. O'Malley, Daniel Kanmert, Jasna Jerecic, Lynn R. Zieske, Henrik Zetterberg, Bradley T. Hyman, Dominic M. Walsh, Dennis J. Selkoe

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number7
JournalAlzheimer's Research and Therapy
Volume7
Issue number1
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

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    Yang, T., O'Malley, T. T., Kanmert, D., Jerecic, J., Zieske, L. R., Zetterberg, H., Hyman, B. T., Walsh, D. M., & Selkoe, D. J. (2015). A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid. Alzheimer's Research and Therapy, 7(1), [7]. https://doi.org/10.1186/s13195-015-0100-y