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

Rapid verification and three-dimensional (3D) mapping of beta-amyloid (A beta) plaques in mouse whole brain is of great significance in early diagnosis of Alzheimer's disease (AD) due to the intricate relationship of A beta plaques with their surrounding microenvironment. Previously reported fluorescent labelling to locate A beta 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 A beta plaques of transgenic (Tg) mouse brain sections into 8 mu m of depth within 1 min. The excellent water-solubility, specificity and sensitivity of AIEgens for A beta plaques enable rapid staining and washing-free imaging of brain sections. The automatic 3D mapping of A beta 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 A beta plaques in mouse whole brain, which would help to explore the correlation between A beta structure and neurodegenerative activity.