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

作者：Yang Ting; O'Malley Tiernan T; Kanmert Daniel; Jerecic Jasna; Zieske Lynn R; Zetterberg Henrik; Hyman Bradley T; Walsh Dominic M^*; Selkoe Dennis J

来源：Alzheimer's Research and Therapy, 2015, 7(1): 14.

DOI：10.1186/s13195-015-0100-y

Introduction: Amyloid beta-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: A beta 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.

• 出版日期2015-3-22
• 单位河北医科大学