Analysis of APR Dimerization in vivo and the impact on neurodegeneration in Alzheimer's Disease

• Applicant: Dr. Simone Eggert
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2006 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 22012210

The ß-amyloid precursor protein (APR) has been the focus of research interest, because it is the precursor to the amyloid ß-protein (Aß), which plays a central role in Alzheimer s Disease pathogenesis. Although the molecular details of Aß generation from APP are being unraveled, the physiological functions of APP are far from clear. It has been proposed that APP may serve as an intermediate in transducing a cell death signal, an activity that may well be related to neuronal dysfunction in AD. It was shown that APP is indeed a substrate for caspases. Importantly, recent results in cultured cells suggest that APP is capable of forming homodimeric complexes, which is accelerated by treatment with Aß, In cultured cells, this APP complex appears to increase the susceptibility to cell death but requires an intact APP cytoplasmic region. These findings led us to propose that one pathway of Aß induced celt death involves complex formation with APP. Our main goal is to investigate in greater detail the impact of homodimerization of APP on the susceptibility to synaptic or neuronal injury in primary hippocampal neurons of rats. Furthermore, we wish to analyze this in vivo by generating a new APP transgenic mouse line wherein APP can be artificially dimerized.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Edward H. Koo