Amyloid-β Oligomers in Cerebrospinal Fluid are Associated with Cognitive Decline in Patients with Alzheimer's Disease

Oligomers of the amyloid-beta peptide (A beta) are thought to be the most toxic form of A beta and are linked to the development of Alzheimer's disease (AD). Here, we used a flow cytometric approach for the detection and assessment of oligomers in cerebrospinal fluid (CSF) from AD patients and other neurological disorders. 30 CSF samples from patients suffering from AD (n=14), non-demented controls (n=12), and other neurological disorders (dementia with Lewy bodies, n=2; vascular dementia, n=1; primary progressive aphasia, n = 1) were analyzed for the presence of A beta-oligomers by flow cytometry. The CSF levels of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-beta (A beta)(42) were determined using ELISA. CSF A beta-oligomer levels in AD patients were elevated in comparison to the non-AD group (p = 0.073). The ratio A beta-oligomers/A beta(42) was significantly elevated in AD subjects compared to non-AD subjects (p=0.001). Most important, there was a negative correlation between the amount of A beta-oligomers and the Mini-Mental Status Exam score (r=-0.65; p=0.013) in AD patients. The detection of A beta-oligomers using flow cytometry analysis seems to be useful in assessing the stage of AD. This is a novel and important finding as none of the currently used CSF biomarkers are clearly associated with dementia severity.