Ultra-sensitive detection of protein biomarkers for early diagnosis of Alzheimer's disease

H-N Chan, D. Xu, S-L Ho, M.S. Wong, H-W Li*
Mind and Tech,
Hong Kong

Keywords: Alzheimer’s disease, Early diagnosis, biomarkers, non-invasive, body fluids


According to the Alzheimer’s Disease Association, there are over 37 million patients currently suffering from AD. Since more people are tended to live into the old age the number is expected to increase 3-fold by 2050.The cost of the medical treatment and the socioeconomic burden are threatened to be overwhelming. Alzheimer’s disease (AD) is the most prevalence cause of dementia, which accounting for over 50% of the cases. Until now the progress in developing a cure for AD is still very disappointing, there is no treatment available to halt or reverse the underlying pathology of AD, only early diagnosis and treatment are the best chance to ameliorate the symptoms of this devastating disease. To date, there is no sensitive and cost-effective method for the quantification of the aforementioned proteins. Capillary electrophoresis, resonance light scattering, surface plasmon resonance, enzyme-linked immunosorbent assay (ELISA), and the polymerase chain reaction (PCR) are the common approaches for peptide detection. However, these methods are limited by the requirements of sophisticated equipment, complicated steps and long assay time, and low sensitivity. To tackle these problems, our research team has developed a direct, rapid, inexpensive, versatile, and ultrasensitive detection assay for the simultaneous quantification of the Ab42, tau and p-tau181 proteins in different biological fluids including cerebrospinal fluid, saliva, serum, and urine. The cost of the newly developed assay is 1–2 orders of magnitude lower than that of the commercially available ELISA kit. Thus, population wide screening and monitoring can be more feasible, which particularly imposes a lower financial burden on developing countries. The detection assay employs magnetic nanoparticles as the purification and preconcentration plat- form. The target analytes are captured by the antibody immobilized on the nanoparticles and labelled by a newly developed turn-on fluorescent dye, SIM. The fluorescent labelled magnetic immunocomplexes are then detected using a fluorescence imaging system. A remarkably low detection limit at the femto- molar level was achieved with minute consumption of the sample (less than 20 mL of the biological fluid for the three AD protein biomarkers) and the results are further validated using INNOTEST ELISA kits. This detection assay can also be per- formed using a commercial spectro-fluorimeter and thus is applicable in a general laboratory setting.