Research project Structure and dynamics of amyloid-β peptide aggregates unraveled by novel infrared spectroscopy appr

(i) Aß oligomers have been correlated with the severity of the disease but their structure is controversial. Here, we will generate structural models of several oligomers in aqueous solu­tion and in interaction with membranes using isotope-edited infrared (IR) spectroscopy. (ii) Lipids are important modulators of Aß aggregation and are elevated in and around plaques. However, their role in plaque development is unclear. Therefore, we will map the biochemical composition of plaques from human brain with higher (20 nm) resolution than before using nanoscale IR spectroscopy.(iii) Little is known about Aß´s interaction with other amyloidogenic polypeptides. This will be studied with a particular focus on structure and morphology of the co-aggregates. For this, we will combine the above approaches.(iv) There is presently no cure for AD but promising anti-amyloid peptides are known. We will study their interaction with Aß as under (iii) for a further knowledge-based improvement of their design.In addition to pioneering methodological development, our approach will further the molecular understanding of AD in areas that are difficult to study with other methods.