Novel BODIPY-Based Fluorescent Probes with Improved Aqueous Solubility for Selective Detection of Soluble Aβ Aggregates

Soluble amyloid β (Aβ) aggregates have attracted attention as therapeutic targets and biomarkers of Alzheimer's disease. We previously reported a fluorescent probe, BAOP-16, which targets soluble Aβ aggregates. However, its limited aqueous solubility has hindered its application in biological assays. In this study, we developed aqueous-soluble fluorescent probes that target soluble Aβ aggregates. Among the synthesized candidates, sBAOP-2-3, which is substituted with two CH₂C^-Tf₂ groups and a diphenyl amino group, exhibited markedly improved aqueous solubility compared with BAOP-16. It also showed a marked increase in fluorescence intensity in the presence of Aβ oligomers, and the highest selectivity for Aβ oligomers over Aβ fibrils. During the aggregation process of Aβ, sBAOP-2-3 detected soluble Aβ aggregates in an early phase. Furthermore, staining experiments using mouse brain sections suggested that sBAOP-2-3 selectively stained soluble Aβ aggregates in mouse brains. These results suggest that sBAOP-2-3 shows promise as a probe for the selective detection of soluble Aβ aggregates in biological systems.