Research article

CD74 interacts with APP and suppresses the production of Aβ

Shuji Matsuda , Yukiko Matsuda and Luciano D'Adamio

Albert Einstein College of Medicine, Department of Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA

author email corresponding author email

Molecular Neurodegeneration 2009, 4:41doi:10.1186/1750-1326-4-41

Published:	22 October 2009

Abstract

Background

Alzheimer disease (AD) is characterized by senile plaques, which are mainly composed of β amyloid (Aβ) peptides. Aβ is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing by β-secretase and γ-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 Aβ. CD74 resembles other APP interacters such as BRI2 and BRI3, since all of them reduce the level of Aβ. However, unlike BRIs, CD74 does not reduce the secretion of sAPPα or sAPPβ. 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 Aβ production by interacting with and derailing normal trafficking of APP.