In vivo evaluation of novel near-infrared fluorescence probe THK565 for imaging amyloid β and tau protein deposits in Alzheimer‘s mouse models

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles. Thus, noninvasive detection of accumulated Aβ and tau in the brain would be beneficial for an early diagnosis of AD. We developed a novel near-infrared fluorescence (NIRF) probe named THK565 for in vivo imaging of Aβ and tau in the brain. In the present study, we evaluated whether THK565 can noninvasively detect Aβ and tau deposits using 2 lines of AD-model mice. We used APP-KI and rTg4510 mice which show progressive accumulation of Aβ and tau in the brain, respectively. Mice were intravenously injected with 0.3 mg/kg of THK565, and then in vivo fluorescence signals were measured using IVIS imaging system at different time point. After in vivo imaging, we harvested brain and confirmed the existence of Aβ and tau deposits by immunohistochemistry.

In vivo NIRF imaging demonstrated higher fluorescent intensity in the brains of APP-KI and rTg4510 than in those of age-matched control mice. The histological analysis confirmed that THK565 clearly labeled Aβ and tau plaques in the brain section. These findings imply that THK565 is useful for noninvasive assessment of Aβ and tau pathology in the brain.