Detection of amyloid peptides: biomarkers for Alzheimer’s Disease and Diabetes

02 December 2020 par Isabelle Frapart
The chemists of the “Metal complexes and MRI” research group have developed novel imaging probes which specifically recognise amyloid aggregates, characteristic of Alzheimer’s Disease and Diabetes and gained new insights into their peptide binding mechanisms. These results could facilitate early diagnosis and better molecular understanding of these diseases.

Metal chelates targeted to amyloid peptides are widely explored as diagnostic tools or therapeutic agents for amyloidogenic diseases. For example, gadolinium complexes can be used as MRI probes, while radiocomplexes (64Cu, 99mTc, etc) can be exploited for nuclear imaging. Other metal complexes capable of preventing aggregate formation are proposed to derive therapeutic strategies.

All these molecules are amphiphilic, composed of a hydrophilic part (containing the metal) and a hydrophobic one (capable of targeting the amyloid aggregates). This particular structure enables the formation of micelles in solution.

The groups of CBM and LCC (Toulouse) have found that this micellisation property has drastic and unexpected consequences on their ability to recognize amyloid peptides and a high impact on their in vivo biodistribution.

The researchers have developed a novel probe with nanomolar affinity towards Aβ and amylin, biomarkers of Alzheimer’s Disease and Ddiabetes, respectively.

This exceptional affinity for a metal complex is only obtained if the complex is present as “single molecule”. Once in the micellar form, this affinity drops by 1000-fold.

These results have a direct consequence for the design of novel imaging and therapeutic probes for amyloidogenic pathologies.

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