Amyloid-beta Oligomers Relate to Cognitive Decline in Alzheimer's Disease

Background: Amyloid-beta (A beta)-oligomers are neurotoxic isoforms of A beta and are a potential diagnostic biomarker for Alzheimer's disease (AD). Objectives: 1) Analyze the potential of A beta-oligomer concentrations in cerebrospinal fluid (CSF) to diagnose and predict progression to AD in a large clinical study sample. 2) Monitor A beta-oligomer concentrations over-time, both in early and advanced stages of AD. 3) Examine the relation between A beta-oligomer levels in CSF and cognitive functioning. Methods: 24 non-demented, 61 mild cognitive impairment (MCI), and 64 AD patients who underwent lumbar puncture and cognitive testing at baseline and follow-up were selected from the memory clinic based Amsterdam Dementia Cohort. CSF samples were analyzed for standard AD-biomarkers and A beta-oligomer levels using a validated in-house A beta-oligomer specific enzyme-linked immunosorbent assay. A beta-oligomer levels were analyzed as indicators of disease progression (follow-up AD diagnosis) and cognitive decline, respectively. Results: Patient groups did not differ in A beta-oligomer concentrations at baseline or follow-up. Baseline CSF A beta-oligomer levels were similar in MCI patients that develop AD as in stable MCI patients. MCI and AD patients showed an annual decrease in A beta-oligomer levels of 9.4% and 6.8%, respectively. A decrease in A beta-oligomer levels over time was strongly associated with more severe cognitive decline in AD patients. Conclusion: Despite the limited diagnostic potential of A beta-oligomer levels in CSF to differentiate between patient groups, and between MCI-AD and MCI-stable patients, changes in CSF A beta-oligomer levels were related to cognitive decline. Therefore, CSF A beta-oligomers may aid in the selection of patients with a more aggressive disease course.