Frontier Research Institute for Interdisciplinary Sciences
Tohoku University

Alzheimer's disease develops through the abnormal aggregation and accumulation of a protein called tau in the brain. The "aggregation patterns (aggregation structures)" of tau exhibit multiple forms, which are closely associated with disease progression and symptom variations. Current diagnostic technologies can only measure "how much tau has increased," but if we could identify "in what form tau aggregates," more precise and earlier diagnosis would become possible.

This research aims to develop unprecedented diagnostic technologies through the interdisciplinary fusion of chemical biology (protein chemical labeling) and nuclear medicine (PET probe chemistry). Principal investigator Associate Professor Shinichi Sato has developed irreversible protein aggregation labeling technology and aims to analyze structural polymorphism of aggregation nuclei using covalently binding probes. Meanwhile, FRIS alumnus Professor Shozo Furumoto (RARiS, Tohoku University) has world-leading achievements in tau-selective PET probe development.

The distinctive feature of this research lies in the fusion of Sato's aggregation-labeling probe concept with Furumoto's tau-selective probe knowledge and compound library. Through (1) protein reactivity evaluation, (2) novel probe molecule design and synthesis, and (3) biological sample evaluation experiments, we will develop technology to identify specific tau aggregation structural polymorphs and create diagnostic drug candidate molecules for early disease diagnosis. The technology capable of identifying structural polymorphism of aggregation nuclei offers new value not found in conventional in vitro diagnostics that only observe quantitative changes in tau, and is achievable for the first time through the fusion of Sato's aggregation-labeling probe concept and Furumoto's tau-selective probe knowledge and compound library. This structural polymorphism identification technology for aggregation nuclei represents a novel value absent in conventional in vitro diagnostics and holds potential for development into early and precision diagnostic technologies.