Fig. 2

Strategies and methods for detecting autolysosomal dysfunction. a Detection of changes in autolysosomal acidification using fluorescent protein reporter (e.g., mRFP-eGFP-LC3) and small-molecule pH probes (e.g., Lysosensor Yellow/Blue). b Monitoring of autolysosomal acidification in vivo through intravital imaging of the reporter mouse brain using multiphoton microscopy. c Positron emission tomography (PET) imaging using protein markers that correlate with autolysosomal dysfunction to detect early onset of neurodegeneration in patients. d Blood- and CSF-based biomarkers that are associated with autolysosomal dysfunction, such as cathepsin level/activity and other molecular signatures obtained from CNS-derived exosomes, are potential early indicators of neurodegeneration. Schematics were created by BioRender.