Fluorescence Chemicals to Detect Insoluble and Soluble Amyloid-β Aggregates

Misfolded amyloid-β (Aβ) is the key biomarker of Alzheimer's disease (AD), and discoveries of fluorescence chemicals visualizing such Aβ aggregates in the brain have made major contributions in postmortem and antemortem diagnosis of the disorder. Insoluble senile plaques of Aβ in brain tissues are commonly stained with thioflavin and congo red dyes and observed through microscopy, while those in living patient brains are detected via radioisotope-labeled fluorescence chemicals for positron emission tomography. Clinical evidence strongly supports the view that plaques are well-associated with the onset but not with the progression of AD. Plaques could accumulate while cognitive functions of at-risk individuals are still intact, and thus, another biomarker is needed to monitor neurodegeneration. Soluble Aβ oligomers are considered to have strong correlation with neuronal loss and brain atrophy as they are the most neurotoxic forms of misfolded Aβ. However, oligomer-targeting probes encounter several major difficulties in development. There is a significant structural distinction between two Aβ species - plaques are β-sheet-rich while oligomers are unordered - and it is still difficult to isolate and stabilize the oligomeric forms of Aβ. Due to these challenges, soluble oligomer-detecting imaging probes are relatively rare compared to the plaque-targeting chemical probes. This Review describes biochemical and optical characteristics of up-to-date fluorescence chemicals targeting insoluble plaques and soluble oligomers of Aβ. We also highlight the contributions of Aβ fluorescence chemicals to the clinical diagnosis of AD and technical challenges in searching for enhanced imaging probes.