1. Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles
- Author
-
Bing Hsien Liu, Che Chuan Yang, Chin-Hsien Lin, Jen Jie Chieh, Herng-Er Horng, Shieh Yueh Yang, Hsin Hsien Chen, and Ming-Jang Chiu
- Subjects
0301 basic medicine ,Adult ,Male ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,High sensitive ,Applied Microbiology and Biotechnology ,law.invention ,03 medical and health sciences ,Magnetics ,0302 clinical medicine ,α-synuclein ,law ,Limit of Detection ,mental disorders ,medicine ,Dementia ,Humans ,Magnetite Nanoparticles ,Aged ,Immunoassay ,medicine.diagnostic_test ,biology ,Chemistry ,Research ,Parkinson Disease ,Middle Aged ,medicine.disease ,Molecular biology ,nervous system diseases ,SQUID ,030104 developmental biology ,nervous system ,Reagent ,biology.protein ,alpha-Synuclein ,Molecular Medicine ,Biomarker (medicine) ,Magnetic nanoparticles ,Female ,Immunomagnetic reduction ,Antibody ,Antibodies, Immobilized ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Background It is difficult to discriminate healthy subjects and patients with Parkinson disease (PD) or Parkinson disease dementia (PDD) by assaying plasma α-synuclein because the concentrations of circulating α-synuclein in the blood are almost the same as the low-detection limit using current immunoassays, such as enzyme-linked immunosorbent assay. In this work, an ultra-sensitive immunoassay utilizing immunomagnetic reduction (IMR) is developed. The reagent for IMR consists of magnetic nanoparticles functionalized with antibodies against α-synuclein and dispersed in pH-7.2 phosphate-buffered saline. A high-Tc superconducting-quantum-interference-device (SQUID) alternative-current magnetosusceptometer is used to measure the IMR signal of the reagent due to the association between magnetic nanoparticles and α-synuclein molecules. Results According to the experimental α-synuclein concentration dependent IMR signal, the low-detection limit is 0.3 fg/ml and the dynamic range is 310 pg/ml. The preliminary results show the plasma α-synuclein for PD patients distributes from 6 to 30 fg/ml. For PDD patients, the concentration of plasma α-synuclein varies from 0.1 to 100 pg/ml. Whereas the concentration of plasma α-synuclein for healthy subjects is significantly lower than that of PD patients. Conclusions The ultra-sensitive IMR by utilizing antibody-functionalized magnetic nanoparticles and high-Tc SQUID magnetometer is promising as a method to assay plasma α-synuclein, which is a potential biomarker for discriminating patients with PD or PDD.
- Published
- 2015