Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer's disease

• Published in: PloS one 2013, Vol.8 (6), p.e66381-e66381
• Main Authors: Hölttä, Mikko, Hansson, Oskar, Andreasson, Ulf, Hertze, Joakim, Minthon, Lennart, Nägga, Katarina, Andreasen, Niels, Zetterberg, Henrik, Blennow, Kaj
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid; Amyloid - cerebrospinal fluid; Amyloid beta-Peptides - cerebrospinal fluid; Biology; Biomarkers; Biomarkers - cerebrospinal fluid; Brain research; Case-Control Studies; Cerebrospinal fluid; Clinical Medicine; Cognitive ability; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnosis; Dementia; Diagnostic systems; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulins; Klinisk medicin; Limit of Detection; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Medicinska och farmaceutiska grundvetenskaper; Memory; Middle Aged; Monoclonal antibodies; Neurochemistry; Neurodegenerative diseases; Neurologi; Neurology; Neurosciences; Neurotoxicity; Neurovetenskaper; Oligomerization; Oligomers; Patients; Peptides; Physiology; Proteins; Psychiatry; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066381

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