A novel near-infrared fluorescence probe THK-565 enables in vivo detection of amyloid and tau deposits in Alzheimer’s disease mouse models

Abstract

Abstract Purpose Non-invasive imaging of amyloid and tau aggregates in the brain is critical for the early diagnosis, disease monitoring, and evaluation of the effectiveness of novel therapies for Alzheimer’s disease (AD). Near-infrared fluorescence (NIRF) imaging with specific probes is a promising technique for in vivo detection of these protein deposits without radiation exposure. Comprehensive screening of fluorescent compounds identified a novel compound THK-565 for in vivo imaging of amyloid-β (Aβ) and tau deposits in the mouse brain. This study assessed whether THK-565 can detect amyloid-β and tau deposits in vivo in AD mouse models.Procedures: The fluorescent properties of THK-565 were evaluated in the presence and absence of Aβ fibrils. APP knock-in (APP-KI) and rTg4510 mice were used as animal models of AD. In vivo NIRF images were acquired after intravenous administration of THK-565 in mice. The binding selectivity of THK-565 to amyloid and tau was evaluated using brain slices from these mouse models.Results The fluorescence intensity of the THK-565 solution was substantially increased by mixing with Aβ fibrils. The maximum emission wavelength of the complex of THK-565 and Aβ fibrils was 704 nm, which was within the range of optical window. In the brain sections from APP-KI and rTg4510 mice, THK-565 selectively bound to amyloid and tau deposits. After intravenous administration of THK-565, the fluorescence signal in the head was significantly higher in APP-KI and rTg4510 mice than in wild-type mice. Ex vivo analysis confirmed that the THK-565 signal corresponded to Aβ and tau immunostaining in the brain sections from these mice.Conclusions A novel NIRF probe, THK-565, enabled in vivo detection of Aβ and tau deposits in the brains of AD mouse models, suggesting that NIRF imaging with THK-565 could non-invasively assess disease-specific pathology in AD.