Multi-modal spectroscopy study of protein aggregation related to Alzheimer’s disease

Important results from the project

The project had two main aims, which can be considered to be in part fulfilled. First, together with beamline scientists from Lund University (LU), we wished to evaluate the suitability of two synchrotron-optimized spectroscopic techniques, X-Ray Fluorescence (XRF) and Fourier Transform InfraRed spectroscopy (FTIR) as a new multimodal screening tool for drugs with anti-aggregating effects. Secondly, using the techniques mentioned above, we aimed to generate valuable unique preclinical data for the participating company ReceptorPharma´s (RPs) drug candidate.

Expected long term effects

In this project, we tested a novel super-resolution infrared imaging technique of SOLEIL and XRF at NanoLab at MAXIV. Importantly, the same spatial resolution of 300 nm was set for both modalities. Thus, using correlative O-PTIR and SXRF, we demonstrated that metal ions and aggregated amyloid beta peptides can be captured in a single nwueon at a nanometer scale in a correlative and complementary manner. This nultimodal synchrotron-based spectroscopic approach can be further developed into a new drug discovery platform and tool for AD and likely as well also for other diseases

Approach and implementation

In the project, we utilized the SMIS- and NanoMAX beamlines at the SOLEIL- and MaxIV synchrotrons respectively, to evaluate synchrotron-based XRF and FTIR in primary neurons from control- and Alzheimer´s disease model mice. By using these two technologies in tandem we were able detect intracellular amyloid aggregates and metal ions inside neurons from disease model mice, but not from control mice, strongly suggesting that the techniques could be important for drug development as they are suitable for identifying and studying the aggregation status of intracellular proteins.