Preparation of near-infrared AIEgen-active fluorescent probes for mapping amyloid-beta plaques in brain tissues and living mice

Fibrillar aggregates of the amyloid-beta protein (A beta) are the main component of the senile plaques found in brains of patients with Alzheimer's disease (AD). Development of probes allowing the noninvasive and high-fidelity mapping of A beta plaques in vivo is critical for AD early detection, drug screening and biomedical research. QM-FN-SO3 (quinoline-malononitrile-thiophene-(dimethylamino)phenylsulfonate) is a near-infrared aggregation-induced-emission-active fluorescent probe capable of crossing the blood-brain barrier (BBB) and ultrasensitively lighting up A beta plaques in living mice. Herein, we describe detailed procedures for the two-stage synthesis of QM-FN-SO3 and its applications for mapping A beta plaques in brain tissues and living mice. Compared with commercial thioflavin (Th) derivatives ThT and ThS (the gold standard for detection of A beta aggregates) and other reported A beta plaque fluorescent probes, QM-FN-SO3 confers several advantages, such as long emission wavelength, large Stokes shift, ultrahigh sensitivity, good BBB penetrability and miscibility in aqueous biological media. The preparation of QM-FN-SO3 takes similar to 2 d, and the confocal imaging experiments for A beta plaque visualization, including the preparation for mouse brain sections, take similar to 7 d. Notably, acquisition and analyses for in vivo visualization of A beta plaques in mice can be completed within 1 h and require only a basic knowledge of spectroscopy and chemistry.