Evaluating Amyloid-beta Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer's Disease

The current study evaluated amyloid-b oligomers (Abo) in cerebrospinal fluid as a clinical biomarker for Alzheimer’s disease (AD). We developed a highly sensitive Abo ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized Ab with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic Abo levels. Three clinical materials of well characterized AD patients (n = 199) and cognitively healthy controls (n = 148) from different clinical centers were included, together with a clinical material of patients with MCI (n = 165). Abo levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased Abo levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable Abo levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own. Citation: Hölttä M, Hansson O, Andreasson U, Hertze J, Minthon L, et al. (2013) Evaluating Amyloid-b Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer’s Disease. PLoS ONE 8(6): e66381. doi:10.1371/journal.pone.0066381 Editor: Sergio T. Ferreira, Federal University of Rio de Janeiro, Brazil Received December 18, 2012; Accepted May 4, 2013; Published June 14, 2013 Copyright: 2013 Hölttä et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by Stiftelsen Gamla tjänarinnor, Gun och Bertil Stohnes stiftelse, Demensfonden, Kungliga och Hvitfeldtska stiftelsen, Stiftelsen Greta Johansson och Brita Anderssons Minnesfond, Adlerbertska stiftelsen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]