Preparation of near-infrared AIEgen-active fluorescent probes for mapping amyloid-β plaques in brain tissues and living mice.
Chenxu YanJianfeng DaiYongkang YaoWei FuHe TianWei-Hong ZhuZhi-Qian GuoPublished in: Nature protocols (2023)
Fibrillar aggregates of the amyloid-β protein (Aβ) 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 Aβ plaques in vivo is critical for AD early detection, drug screening and biomedical research. QM-FN-SO 3 (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 Aβ plaques in living mice. Herein, we describe detailed procedures for the two-stage synthesis of QM-FN-SO 3 and its applications for mapping Aβ plaques in brain tissues and living mice. Compared with commercial thioflavin (Th) derivatives ThT and ThS (the gold standard for detection of Aβ aggregates) and other reported Aβ plaque fluorescent probes, QM-FN-SO 3 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-SO 3 takes ~2 d, and the confocal imaging experiments for Aβ plaque visualization, including the preparation for mouse brain sections, take ~7 d. Notably, acquisition and analyses for in vivo visualization of Aβ plaques in mice can be completed within 1 h and require only a basic knowledge of spectroscopy and chemistry.
Keyphrases
- living cells
- fluorescent probe
- high resolution
- high fat diet induced
- single molecule
- blood brain barrier
- gene expression
- quantum dots
- white matter
- coronary artery disease
- healthcare
- fluorescence imaging
- high density
- label free
- insulin resistance
- metabolic syndrome
- multiple sclerosis
- wild type
- molecular docking
- skeletal muscle
- cognitive decline
- loop mediated isothermal amplification
- binding protein
- adipose tissue
- brain injury
- nucleic acid
- raman spectroscopy
- structure activity relationship