Structural basis of biological active β-amyloid conformers

• Applicants: Professor Dr. Marcus Fändrich; Professor Dr. Mathias Jucker
• Subject Area: Biochemistry ; Molecular and Cellular Neurology and Neuropathology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409798861

The deposition of beta-amyloid (Abeta) peptide as amyloid fibrils is ahallmark of neurodegenerative conditions, such as cerebral amyloidangiopathy (CAA) and Alzheimer´s disease (AD). Underlying theseevents is a molecular self-assembly reaction that can be seeded invitro by preformed amyloid fibrils and in vivo by intracerebral injectionof Abeta-containing brain extracts into Alzheimer mouse models.Increasing evidence shows that this effect is provoked by Abeta fibril.Abeta fibrils may also play a pathogenic role in CAA, althoughneurodegeneration in AD may rather depend on the toxic effect ofintermediate states. Conflicting structural models have been obtainedfor different preparations of Abeta fibrils or intermediates in vitro, whilethe structure of Abeta fibrils formed inside a diseased patient remainunclear. In this project we will purify Abeta fibrils from diseased humantissue to make it available for direct structural analysis with high end biophysical methods, including in particular electron microscopy.Expected results may be important for understandning the spreadingof neurodegenerative diseases.

• DFG Programme: Research Grants