Detection of misfolded proteins in neurodegenerative disease models with a highly sensitive chemiluminescence probe

Visualizing misfolded proteins would greatly facilitate early diagnosis, etiology elucidation, and therapy monitoring of neurodegeneration. Although several probes have been reported, simple and versatile detection in vivo is still challenging. We demonstrated that both generic and precise detection of misfolded proteins could be achieved with a chemiluminescence probe, ADLumin-1. For the generic aspect, ADLumin-1 was highly sensitive to various misfolded proteins, showing up to 127.73-fold higher signal-to-noise ratio than Thioflavin T. ADLumin-1 could also non-invasively visualize misfolded proteins in mouse models of Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Furthermore, ADLumin-1 displayed precise detection value for α-synuclein by combining with PMCA in vitro and bioorthogonal ChRET imaging technology in vivo. ADLumin-1 can selectively detect α-synuclein in CSF at the femtomolar level and enables in situ monitoring of misfolded α-synuclein in vivo. Combining generality and precision, our findings could be widely applied in preclinical and clinical studies of neurodegenerative diseases.