Fluorescent and Scanometric Ultrasensitive Detection Technologies with the Bio-Bar Code Assay for Alzheimer's Disease DiagnosisPublic Deposited
Alzheimer’s disease (AD) is a progressive mental disorder that affects 23 million people worldwide. It is pathologically characterized by amyloid plaques and tau tangles that form in the brain. The hard, insoluble amyloid plaques develop from the naturally secreted amyloid beta peptide, which can also assemble into toxic oligomeric forms known as amyloid beta derived diffusible ligands (ADDL). Currently, with no cure or a 100 percent accurate diagnostic method for AD, the potential for preventive medicine is limited. The presence of soluble ADDL in biological fluids of Alzheimer’s patients, however, provides a promising biomarker for the use in detection. The application of functionalized nanoparticle technology in the use of protein detection, in this case ADDL, can be used for Alzheimer’s disease detection. The ultrasensitive nature of this technique developed by the Mirkin lab, termed the biobar code assay, provides new hope for diagnosis. Using nanoparticles and magnetic microparticles functionalized with ADDL antibodies, this assay will allow for early diagnosis before irreversible brain damage has occurred. The sensitivity of the assay relies on an amplification step that results in thousands of DNA strands for each target protein. In conjunction with the bio-bar code assay, fluorescent and scanometric detection methodologies were used to detect the neurotoxic synthetic ADDL. Fluorescent detection was found to be highly quantitative but was not as sensitive as the scanometric method. The possibility of improving the sensitivity of fluorescent detection can be further explored using a fluorophore Alexa-488 tagged bar-code DNA. The sensitivity of the scanometric method proved useful in showing a difference in plasma ADDL levels between Alzheimer’s patients and control samples, providing a promising beginning for the early detection and diagnosis of this debilitating neurodegenerative disease.