Related Experiment Video
Updated: Feb 15, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
APP intracellular domain-WAVE1 pathway reduces amyloid-β production
Ilaria Ceglia1, Christiane Reitz2,3,4,5, Jodi Gresack1
1Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Abstract:
An increase in amyloid-β (Aβ) production is a major pathogenic mechanism associated with Alzheimer's disease (AD), but little is known about possible homeostatic control of the amyloidogenic pathway. Here we report that the amyloid precursor protein (APP) intracellular domain (AICD) downregulates Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 1 (WAVE1 or WASF1) as part of a negative feedback mechanism to limit Aβ production. The AICD binds to the Wasf1 promoter, negatively regulates its transcription and downregulates Wasf1 mRNA and protein expression in Neuro 2a (N2a) cells. WAVE1 interacts and colocalizes with APP in the Golgi apparatus. Experimentally reducing WAVE1 in N2a cells decreased the budding of APP-containing vesicles and reduced cell-surface APP, thereby reducing the production of Aβ. WAVE1 downregulation was observed in mouse models of AD. Reduction of Wasf1 gene expression dramatically reduced Aβ levels and restored memory deficits in a mouse model of AD. A decrease in amounts of WASF1 mRNA was also observed in human AD brains, suggesting clinical relevance of the negative feedback circuit involved in homeostatic regulation of Aβ production.
Related Concept Videos
TGF - β Signaling Pathway
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid Fibrils
Intracellular Signaling Cascades
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
C4 Pathway and CAM
C4 Pathway
The C4 pathway is used by plants such as...

