Advances in targeted tracking and detection of soluble amyloid-β aggregates as a biomarker of Alzheimer's disease

Misfolding and aggregation of amyloid-β (Aβ) peptides are key hallmarks of Alzheimer's disease (AD). With accumulating evidence suggesting that different Aβ species have varied neurotoxicity and implications in AD development, the discovery of affinity ligands and analytical approaches to selective distinguish, detect, and monitor Aβ becomes an active research area. Remarkable advances have been achieved, which not only promote our understanding of the biophysical chemistry of the protein aggregation during neurodegeneration, but also provide promising tools for early detection of the disease. In view of this, we summarize the recent progress in selective and sensitive approaches for tracking and detection of Aβ species. Specific attentions are given to soluble Aβ oligomers, due to their crucial roles in AD development and occurrence at early stages. The design principle, performance of targeting units, and their cooperative effects with signal reporters for Aβ analysis are discussed. The applications of the novel targeting probes and sensing systems for dynamic monitoring oligomerization, measuring Aβ in biosamples and in vivo imaging in brain are summarized. Finally, the perspective and challenges are discussed regarding the future development of Aβ-targeting analytical tools to explore the unknown field to contribute to the early diagnosis and treatment of AD.