Metal-based Agents for Selective Amyloid Imaging – MASAI

Amyloid aggregates are associated with many pathologies, like Alzheimers’s disease (AD) or Type 2 diabetes (T2DM), respectively involving Abeta and amylin. Recent evidence indicates a link between these two diseases, likely mediated by “cross-seeding” processes when one amyloid protein promotes aggregation of another. We identified the first metal complexes selective for amylin vs Abeta fibrils, and here we propose to i) improve their selectivity via rational molecular design, ii) investigate their peptide binding affinities, and iii) exploit their potential as imaging agents for selective MRI or SPECT visualisation of amyloid peptides in ex vivo tissue samples and preclinical models. These probes will help establish the role of peptide cross-seeding as the link between T2DM and AD. Ultimately, these results may explain why i) the presence of multiple amyloid proteins in tissues leads to exacerbation of clinical features, and ii) one amyloid disease is a risk factor for development of another.