In Vivo Near-Infrared Fluorescence Imaging Selective for Soluble Amyloid β Aggregates Using y-Shaped BODIPY
Takahiro Akasaka1, Hiroyuki Watanabe1, Masahiro Ono1
1Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Abstract:
Soluble amyloid β (Aβ) aggregates, suggested to be the most toxic forms of Aβ, draw attention as therapeutic targets and biomarkers of Alzheimer's disease (AD). As soluble Aβ aggregates are transient and diverse, imaging their diverse forms in vivo is expected to have a marked impact on research and diagnosis of AD. Herein, we report a near-infrared fluorescent (NIRF) probe, BAOP-16, targeting diverse soluble Aβ aggregates. BAOP-16, whose molecular shape resembles "y", showed a marked selective increase in fluorescence intensity upon binding to soluble Aβ aggregates in the near-infrared region and a high binding affinity for them. Additionally, BAOP-16 could detect Aβ oligomers in the brains of Aβ-inoculated model mice. In an in vivo fluorescence imaging study of BAOP-16, brains of AD model mice displayed significantly higher fluorescence signals than those of wild-type mice. These results indicate that BAOP-16 could be useful for the in vivo NIRF imaging of diverse soluble Aβ aggregates.


