title: A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School Boston, 77 Avenue Louis Pasteur, Harvard Institute Medical, Room 730, Boston, MA 02115 USA.
authors: Ting
authors: T
authors: Yang
authors: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School Boston, 77 Avenue Louis Pasteur, Harvard Institute Medical, Room 730, Boston, MA 02115 USA.
authors: Tiernan T
authors: TT
authors: O'Malley
authors: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School Boston, 77 Avenue Louis Pasteur, Harvard Institute Medical, Room 730, Boston, MA 02115 USA.
authors: Daniel
authors: D
authors: Kanmert
authors: Acumen Pharmaceuticals, Inc., 9816 Easton Drive, Beverly Hills, CA 90210 USA.
authors: Jasna
authors: J
authors: Jerecic
authors: Singulex, Inc., 1701 Harbor Bay Parkway, Suite 200, Alameda, CA USA.
authors: Lynn R
authors: LR
authors: Zieske
authors: Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden ; UCL Institute of Neurology, Queen Square, London, WC1N 3BG UK.
authors: Henrik
authors: H
authors: Zetterberg
authors: Massachusetts General Hospital, Charlestown, MA 02129 USA.
authors: Bradley T
authors: BT
authors: Hyman
authors: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School Boston, 77 Avenue Louis Pasteur, Harvard Institute Medical, Room 730, Boston, MA 02115 USA.
authors: Dominic M
authors: DM
authors: Walsh
authors: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School Boston, 77 Avenue Louis Pasteur, Harvard Institute Medical, Room 730, Boston, MA 02115 USA.
authors: Dennis J
authors: DJ
authors: Selkoe