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

The current study evaluated amyloid-beta oligomers (A beta o) in cerebrospinal fluid as a clinical biomarker for Alzheimer's disease (AD). We developed a highly sensitive A beta o 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 A beta with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic A beta o 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). A beta o 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 A beta o levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable A beta o 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.