Abstract

Alzheimer’s Disease (AD), an incurable neurodegenerative disorder is characterized by irreversible deposition of amyloid plaques and fibrillary tangles as well as progressive memory and cognitive decline. Amyloid-𝛃 (A𝛃) peptides, Tau, and neurofilament light (NfL) proteins in cerebral spinal fluid (CSF) are considered useful biomarkers for AD¹. Numerous studies have shown that soluble A𝛃₄₂ oligomers are more neurotoxic and also be found in circulatory body fluids^{2, 3}. The conventional enzyme-linked immunosorbent assay (ELISA) is a widely adopted for quantification the AD biomarkers including A𝛃 oligomers. However, the sensitivity of ELISA is not satisfactory for the detection of low-abundance of such biomarkers in the early stage of AD. In this work, we have developed an ultrasensitive, cost-efficient, and reliable method for the quantification of A𝛃₄₂ oligomers in a few µL body fluids (CSF and serum). This assay is based on a specific antibody-antigen immunoreaction and formation of immuno-sandwich complexes on magnetic nanoparticles followed by labeling of the target protein with a tailor-made cyanine-based turn-on fluorophore, named SPM. Our initial results demonstrated that the detection limit of the sensitive assay reached 10^-3 ng/mL. This assay holds great potential for diagnosing AD at the early stage.

Reference

1. Jamerlan, A.; An, S. S. A.; Hulme, J. TrAC Trends in Analytical Chemistry 2020, 129, 115919.
2. Ahmed, M., Davis, J., Aucoin, D. et al. Nature Structural & Molecular Biology 2010, 17 (5), 8.
3. Cizas, P.; Budvytyte, R.; Morkuniene, R.; Moldovan, R.; Broccio, M.; Lösche, M.; Niaura, G.; Valincius, G.; Borutaite, V. Archives of Biochemistry and Biophysics 2010, 496 (2), 84–92.