CHAPTER 4 A - oligomers quantification in CSF , and their clinical value

Objectives 1) Analyze the potential of amyloid beta (A)-oligomer concentrations in cerebrospinal fluid (CSF) to diagnose and predict progression to Alzheimer's disease (AD) in a large clinical study sample. 2) Monitor A-oligomer concentrations overtime , both in early and advanced stages of AD. 3) Examine the relation between A-oligomer levels in CSF and cognitive functioning. Methods 24 Non-demented, 61 mild cognitive impairment 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-oligomer levels using a validated in-house A-oligomer specific enzyme-linked immunosorbent assay. A-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-oligomer concentrations at baseline or follow-up. Baseline CSF A-oligomer levels were similar in MCI patients that develop AD as in stable MCI patients. Interestingly, both MCI and AD patients showed an annual decrease in A-oligomer levels of 9.4% and 6.8%, respectively. A decrease in A-oligomer levels over time was strongly associated with more severe cognitive decline in AD patients. Conclusion Despite the limited diagnostic potential of A-oligomer levels in CSF to differentiate between patient groups, and between MCI-AD and MCI-stable patients, changes in CSF A-oligomer levels were related to cognitive decline. Therefore, CSF A-oligomers may aid in the selection of patients with a more aggressive disease course.