Enhanced Detection Specificity and Sensitivity of Alzheimer's Disease Using Amyloid-β-Targeted Quantum Dots

Diagnostics of Alzheimer's disease (AD) commonly employ the use of fluorescent thioflavin derivatives having affinity for the amyloid-β (Aβ) proteins associated with AD progression. However, thioflavin probes have limitations in their diagnostic capabilities arising from a number of undesireable qualities, including poor photostability, weak emission intensity, and high emission overlap with the backgound tissue autofluorescence. To overcome such limitations, we have developed nanoformulated probes consisting of a red-emitting fluorescent quantum dot (QD) core encapsulated in a PEGylated shell with benzotriazole (BTA) targeting molecules on the surface (QD-PEG-BTA). The combination of strong red fluorescence, multivalent binding, and decreased backgound signal and nonspecific binding provided the ability of the QD-PEG-BTA probes to achieve detection sensitivites 4 orders of magnitude greater than those of conventional thioflavin derivatives. This study opens the door for the use of QDs in AD detection applications.