AICD and Arc overexpression in drosophila increase APP cleavage and promotes aggregates in the brain 

Abnormal amyloid precursor protein (APP) processing, specifically cleavage through the amyloidogenic pathway, creates amyloid-beta proteins that, when oligomerized, cause brain damage and are a hallmark of Alzheimer’s disease. Here, we examined how AICD and Arc expression affect APP localization and processing in Drosophila. Immunohistochemistry revealed that AICD overexpression induced Arc ex- pression and led to APP clustering and accumulation,  which were not present in controls.   Western  blot analysis showed that Arc-GFP expression generated additional APP-related species, possibly by- products of APP proteolysis.  This included AICD, which drives the feed-forward loop in APP cleav-  age and Alzheimer’s disease. Furthermore, long-term memory (LTM) training increased APP cleavage in MBON5β neurons, which in turn caused increased AICD and sAPP levels. These findings suggest that Arc and AICD are the main components in APP proteolysis, and memory-related activity further drives the feedforward loop in vivo.