Background: It is difficult to discriminate healthy subjects and patients with Parkinson disease (PD) or Parkinson\ndisease dementia (PDD) by assaying plasma �±-synuclein because the concentrations of circulating �±-synuclein in the\nblood are almost the same as the low-detection limit using current immunoassays, such as enzyme-linked immunosorbent\nassay. In this work, an ultra-sensitive immunoassay utilizing immunomagnetic reduction (IMR) is developed.\nThe reagent for IMR consists of magnetic nanoparticles functionalized with antibodies against �±-synuclein and\ndispersed in pH-7.2 phosphate-buffered saline. A high-Tc superconducting-quantum-interference-device (SQUID)\nalternative-current magnetosusceptometer is used to measure the IMR signal of the reagent due to the association\nbetween magnetic nanoparticles and �±-synuclein molecules.\nResults: According to the experimental �±-synuclein concentration dependent IMR signal, the low-detection\nlimit is 0.3 fg/ml and the dynamic range is 310 pg/ml. The preliminary results show the plasma �±-synuclein for\nPD patients distributes from 6 to 30 fg/ml. For PDD patients, the concentration of plasma �±-synuclein varies from\n0.1 to 100 pg/ml. Whereas the concentration of plasma �±-synuclein for healthy subjects is significantly lower\nthan that of PD patients.\nConclusions: The ultra-sensitive IMR by utilizing antibody-functionalized magnetic nanoparticles and high-Tc SQUID\nmagnetometer is promising as a method to assay plasma �±-synuclein, which is a potential biomarker for discriminating\npatients with PD or PDD.
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