AIE-based fluorescent micro-optical sectioning tomography for automatic 3D mapping of β-amyloid plaques in Tg mouse whole brain

Abstract

Rapid verification and three-dimensional (3D) mapping of β-amyloid (Aβ) plaques in mouse whole brain is of great significance in early diagnosis of Alzheimer’s disease (AD) due to the intricate relationship of Aβ plaques with their surrounding microenvironment. Previously reported fluorescent labelling to locate Aβ plaques usually require lengthy permeation/staining/washing procedures to eliminate non-specific binding and improve fluorescence signal-to-noise ratio, which is inaccessible to automatic brain wide 3D imaging. Here we report a kind of water-soluble fluorescent probes with aggregation-induced emission (AIE) activities, named AIEgens, which can rapidly permeate and stain Aβ plaques of transgenic (Tg) mouse brain sections into 8 μm of depth within 1 min. The excellent water-solubility, specificity and sensitivity of AIEgens for Aβ plaques enable rapid staining and washing-free imaging of brain sections. The automatic 3D mapping of Aβ plaques in Tg mouse’s whole brain is implemented through the cycling process of in situ real-time mechanical sectioning, staining and imaging with AIEgens in fluorescent micro-optical sectioning tomography (fMOST) system. The AIE-based fMOST, which integrates the in-situ staining/imaging/sectioning steps of Tg mouse’s whole brain, provides an automatic 3D mapping solution to access the size, morphology and 3D distribution of Aβ plaques in mouse whole brain, which would help to explore the correlation between Aβ structure and neurodegenerative activity.