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A more recent version of this article appeared on January 1, 2007
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Submitted on April 7, 2006
Revised on August 14, 2006
Accepted on October 26, 2006
¶
*Institute of Pathology and Neuropathology, University Hospital Essen, D-45122 Essen, Germany; Department of Physiology and Medical Physics and RCSI Neuroscience Research Centre, Royal College of Surgeons in Ireland, Dublin 2, Ireland; ||Experimental Neurosurgery, Center for Neurology and Neurosurgery, Johann Wolfgang Goethe University Clinics Frankfurt, D-60590 Frankfurt, Germany; Medical Proteome-Center, Ruhr-University Bochum, D-44780 Bochum, Germany; Institute of Neuropathology, University Hospital Muenster, D-48149 Muenster, Germany
Monitoring Editor: Paul Forscher
Amyloidogenic processing of the amyloid precursor protein (APP) results in the generation of 
-amyloid, the main constituent of Alzheimer plaques, and the APP intracellular domain (AICD). Recently, it has been demonstrated that AICD has transactivation potential, however, the targets of AICD dependent gene regulation and hence the physiological role of AICD remain largely unknown. We analyzed transcriptome changes during AICD dependent gene regulation using a human neural cell culture system inducible for expression of AICD, its coactivator FE65, or the combination of both. Induction of AICD was associated with increased expression of genes with known function in the organization and dynamics of the actin cytoskeleton including 
2-Actin and Transgelin (SM22). AICD target genes were also found to be differentially regulated in the frontal cortex of AD patients compared with controls as well as in AICD/FE65 transiently transfected murine cortical neurons. Confocal image analysis of neural cells and cortical neurons expressing both AICD and FE65 confirmed pronounced changes in the organization of the actin cytoskeleton including the destabilisation of actin fibers and clumping of actin at the sites of cellular outgrowth. Our data point to a role of AICD in developmental and injury-related cytoskeletal dynamics in the nervous system.
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