Blood-Brain Barrier-Permeable Dual-Responsive Fluorescent Probe Reveals an Increased Risk of Alzheimer's Disease in Diabetic Patients.

Alzheimer's disease (AD) is a global concern, and revealing its early diagnostic signals is crucial for timely intervention and treatment. Fluorescent probes hold great promise in disease diagnosis due to their high sensitivity and specificity. However, most existing probes struggle to effectively penetrate the blood-brain barrier (BBB), which significantly limits their application in brain disease imaging, including AD. Herein, a novel BBB-permeable fluorescent probe CL was reported. CL contains a quinolinium group and a C12 alkyl chain, enabling it to effectively target mitochondria without being affected by mitochondrial membrane potential. CL exhibits a dual response to viscosity and ONOO-, displaying sensitive fluorescence responses at 812 and 495 nm, respectively. These characteristics enable CL to simultaneously monitor fluctuations in mitochondrial viscosity and ONOO-, thereby achieving dual-channel detection and providing more comprehensive pathological information. More importantly, compared with the control probe DL containing a short C1 chain, CL exhibits superior BBB penetration ability and efficient brain imaging performance. Utilizing CL, alterations in viscosity and ONOO- in the brains of AD and diabetes mice were successfully monitored. The results not only show that both viscosity and ONOO- are important biomarkers of brain diseases but also reveal that diabetes patients have a higher risk of AD, laying a foundation for AD diagnosis and prevention.