Alzheimer’s disease (AD) has become the most common form of dementia in humans. Amyloid depositions in the brains of affected patients are of central importance for the disease progression, which inevitably leads to neuronal death. In the past we have determined the 3D structure of Alzheimers Ab(1-42) fibrils that were generated in vitro. However, it is currently unclear whether these fibrils correspond to those deposited in AD brains, or whether all AD patients contain the same type of deposits. Therefore we are interested in the 3D structures of brain derived AD fibrils.

In this project, recombinant Alzheimer’s peptide Ab(1-42) will be produced E. coli using an established purification protocol. The monomeric recombinant Ab(1-42) will then be converted into fibrillar aggregates using brain derived material as templates (“seeds”). The establishment of the necessary seeding procedure will be an essential part of this master-thesis project. It is the aim to obtain sufficient yields for a 3D structure investigation by NMR techniques. The knowledge of native fibrillar 3D structures will be a crucial milestone to understand the molecular mechanism underlying AD, and will thus also provide clues for novel therapeutic targets.

The successfull candidate will be introduced into all essential molecular biological and protein biochemical techniques. The obtained products will be first characterized by multiple biophysical techniques including fluorescence, CD-spectroscopy, fourier transformed infrared spectroscopy and light scattering. The functionality of the obtained amyloid fibrils will be investiagetd using AD mouse models.