title: Discovery of boronic acid-based fluorescent probes targeting amyloid-beta plaques in Alzheimer's disease.
abstract: A boronic acid-based fluorescent probe was developed for diagnosis of amyloid-β (Aβ) plaques from Alzheimer's disease (AD). Probe 4c, which included boronic acid as a functional group, exhibited a significant increase (64.37-fold, FAβ/F0) in fluorescence intensity as a response to Aβ aggregates, with a blue shift (105nm) in the maximum emission wavelength. We found that boronic acid as a functional group improved the binding affinity (KD value=0.79±0.05μM for 4c) for Aβ aggregates and confirmed that 4c selectively stained Aβ plaques in brain sections from APP/PS1 mice. Ex vivo fluorescence imaging using mice (normal and APP/PS1) also revealed that 4c was able to penetrate the blood-brain barrier (BBB) and to stain Aβ plaques in the brain. From these results, we believe that 4c will be useful as a fluorescent probe in preclinical research related to AD. Furthermore, we believe that our results with boronic acid also provide valuable information for the development of a probe for Aβ plaques.
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Jung
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University, 501 Jinju Daero, Jinju 660-701, Republic of Korea.
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea; Department of Radiation Biotechnology and Applied Radioisotope Science, Korea University of Science and Technology, Daejeon 34113, Republic of Korea.
authors.forename: Jongho
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Seung Dae
authors.initials: SD
authors.lastname: Yang
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Hur
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea; Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea. Electronic address: ydpark@kaeri.re.kr.
authors.forename: Yong Dae
authors.initials: YD
authors.lastname: Park
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000032:analysis*; D000818:Animals; D001897:Boronic Acids / Q000737:chemistry* / Q000493:pharmacokinetics; D001921:Brain / Q000473:pathology*; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D061848:Optical Imaging / Q000379:methods; D058225:Plaque, Amyloid / Q000175:diagnosis* / Q000473:pathology; D066263:Protein Aggregation, Pathological / Q000175:diagnosis / Q000473:pathology
chemical_list: D016564:Amyloid beta-Protein Precursor; D001897:Boronic Acids; D005456:Fluorescent Dyes
keywords: Alzheimer’s disease (AD); Amyloid plaque; Boronic acid; Fluorescent probe