Abstract
BackgroundAlzheimer 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.ResultsHere, 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.ConclusionTaken together, we propose that CD74 inhibits Aβ production by interacting with and derailing normal trafficking of APP.
Highlights
About 1% of humans aged 60-64 years have Alzheimer disease (AD), increasing steadily to as many as 35%-40% after age 85 [1]
Taken together, we propose that CD74 inhibits Aβ production by interacting with and derailing normal trafficking of amyloid precursor protein (APP)
Little is known about the relationship between CD74 and APP. Because both BRI2 and BRI3 interact with APP and inhibits APP processing [2022,26], we investigated the role of CD74 in regulating the processing of APP
Summary
About 1% of humans aged 60-64 years have AD, increasing steadily to as many as 35%-40% after age 85 [1]. AD progressively leads to a severely impaired state and complete social dependence. Cerebral atrophy, neurofibrillary tangles and amyloid plaques are observed in the hippocampus, entorhinal cortex, amygdala and other areas. Tangles consist of intraneuronal masses of helically wound filaments of the hyperphosphorylated protein, tau. Plaques are extracellular deposits of Aβ, a peptide derived from cleavage of APP, surrounded by dystrophic neurites. Most AD cases present Aβ deposits in cortical and/or meningeal micro vessels. In a minority of cases, this vascular cerebral amyloid angiopathy (CAA) is rather severe [2]. 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
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