CD74 interacts with APP and suppresses the production of A

Abstract

Background. Alzheimer disease (AD) is characterized by senile plaques, which are mainly composed of amyloid (A) peptides. A is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing by -secretase and -secretase. Results. Here, we show that CD74, the invariant chain of class II major histocompatibility complex, interacts with APP and serves as a negative regulator of A. CD74 resembles other APP interacters such as BRI2 and BRI3, since all of them reduce the level of A. However, unlike BRIs, CD74 does not reduce the secretion of sAPP or sAPP. Interestingly, in HeLa cells, over expression of CD74 steers APP, but not Notch, to large vacuoles created by CD74. Conclusion. Taken together, we propose that CD74 inhibits A production by interacting with and derailing normal trafficking of APP.