Microscope-Free Microdissection of Amyloid Plagues in Alzheimer’s Disease Tissue via Single Electron Transfer Photocatalysis

ABSTRACT: Amyloid protein deposit, like Aβ plaques, is a pathological hallmark of Alzheimer’s disease (AD). While plenty of amyloid imaging reagents available for diagnosis, their composition associated with disease etiology is challenging to analyze in intact tissue sample. Herein, we report an amyloid-targeting probe to photocatalyze in-situ labeling and profiling of Aβ plaques in AD brain tissue via single electron transfer (SET) mechanism. First, we render this amyloid probe with photocatalytic labeling function by fragment fusion of classical scaffolds of fluorescent amyloid sensors. Second, we demonstrate its labeling selectivity to amyloid proteins over monomer counterparts. Mechanistically, we show spatially resolved labeling is driven by the short-lived SET photocatalytic process. Finally, we use this probe to capture and profile the composition of amyloid plagues in Alzheimer’s disease brain tissue. Surpassing other AD proteomics datasets, our work spatially resolves pathogenic Aβ and typical AD biomarkers as top-ranked hits. Together, the short-lived SET-driven photocatalysis spatially restrains protein labeling to occur in ultra-proximity to amyloids, allowing for microscope-free amyloid tissue microdissection at molecular level.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: 夏 秋璇  

LAB HEAD: Yu Liu

PROVIDER: PXD059374 | Pride | 2025-01-13

REPOSITORIES: pride