Detection of Amyloid-β Oligomers in Human Cerebrospinal Fluid by Flow Cytometry and Fluorescence Resonance Energy Transfer

Abstract

The neuropathology of Alzheimer's disease (AD) has been linked recently to non-fibrillar forms of neurotoxic amyloid-β (Aβ) oligomers of which high levels are observed in the brain of AD patients. This suggests that Aβ oligomers play a key role in the early events of AD, underlining their potential for the early diagnosis of the disease. We have developed an extremely sensitive assay for the detection of oligomeric and fibrillar structures of Aβ that is based on multiparametric analysis of data obtained by flow cytometry and fluorescence resonace energy transfer (Fret). The assay readily detects Aβ oligomers in human cerebrospinal fluid (CSF) as verified by dot blot of the isolated particles. By measuring 174 CSF samples of non-demented control patients with various neurological disorders a high reliability and reproducibility of the method could be demonstrated.