Early diagnostics at the preclinical stage of Alzheimer's disease is of utmost importance for drug development in clinical trials and prognostic guidance. Since soluble A beta oligomers are considered to play a crucial role in the disease pathogenesis, several methods aim to quantify A beta oligomers in body fluids such as cerebrospinal fluid (CSF) and blood plasma. The highly specific and sensitive method surface-based fluorescence intensity distribution analysis (sFIDA) has successfully been established for oligomer quantitation in CSF samples. In our study, we explored the sFIDA method for quantitative measurements of synthetic Aa particles in blood plasma. For this purpose, EDTA-, citrate-and heparin-treated blood plasma samples from five individual donors were spiked with Aa coated silica nanoparticles (A beta-SiNaPs) and were applied to the sFIDA assay. Based on the assay parameters linearity, coefficient of variation and limit of detection, we found that EDTA plasma yields the most suitable parameter values for quantitation of Aa oligomers in sFIDA assay with a limit of detection of 16 fM.