Amyloid-ID: photocatalytic profiling of amyloid deposits in Alzheimer's disease tissue.

Abstract

Deposition of amyloid proteins and their associated interactome is a hallmark of Alzheimer's disease (AD) and other amyloidosis diseases, with their composition implying disease etiology. However, precise in-situ micro-dissection of amyloid deposits in AD brain tissue remains a challenge. In this work, we first divert the excited state energy of Thioflavin T from singlet fluorescence to triplet photocatalytic amyloid protein labeling through molecular engineering, while maintain its pan-amyloid binding affinity and selectivity. We further demonstrate that the amyloid labeling is catalyzed via type-I radical-based photosensitization with diverse residue modification sites. In female AD mouse brain tissue without homogenization, Amyloid-ID in-situ captures and profiles amyloid deposits, reliably reporting the often-lost tau biomarker. Finally, we provide comparative amyloidomics resources across 3 commonly used AD mouse models, revealing conjunct mitochondrial entangling pattern within amyloid deposits. Overall, we report a photocatalytic proteomics strategy (namely Amyloid-ID) to profile amyloid deposits directly from AD brain tissue.