LC-MSMS of the brain in mice with Alzheimer's disease

The spatiotemporal progression of amyloid protein pathology in Alzheimer's disease (AD) is region-specific, but traditional analytical methods have difficulty in resolving the differences in plaque composition in different brain regions. In this study, a photosensitive probe P5 based on engineered Congo red derivatives was developed. Its specific photocatalytic properties of binding amyloid proteins can achieve precise microdissection of brain slice plaques and subsequent proteomic analysis. Verified by the AD mouse model, this method successfully identified the core biomarkers in hippocampal and cortical sediments. Comparative proteomics revealed significant component overlap in amyloid deposition in the two regions and suggested the key role of the silk autophagy-lysosomal pathway in the pathogenesis of AD. This study provides a new methodological strategy for analyzing region-specific amyloid heterogeneity and its pathological mechanism.