APP intracellular domain–WAVE1 pathway reduces amyloid-β production

The intracellular domain of amyloid precursor protein (AICD), generated during the processing of APP along the amyloidogenic pathway, is shown to repress transcription of the Wasf1 gene, encoding the WAVE1 protein. The reduction in WAVE1 levels inhibits cell surface trafficking of APP, thereby creating a homeostatic negative feedback circuit to limit further production of amyloid-β.