The effect of high glucose on APP metabolism and Abeta production
AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by a
progressive decline in memory and cognitive functions. It is the leading cause of dementia.
Abnormal accumulation and deposition of amyloid-β protein (Aβ) to form plaques is a
pathological hallmark of AD. Aβ, the major component of plaques, derives from sequential
cleavage of amyloid-β precursor protein (APP) by β-secretase and γ-secretase. Dysregulation of
APP processing and Aβ generation is believed to play an essential role in the pathogenesis of
Diabetes is a complex metabolic disorder characterized by chronic hyperglycemia.
Epidemiological studies revealed an elevated risk of developing AD in people with diabetes.
However, the underlying mechanisms remain unknown. To identify the role of diabetes in AD
pathogenesis, the effect of high glucose on APP metabolism and Aβ generation was investigated
using cultured human neuroblastoma cells. In this study, we clearly showed that high glucose
treatment significantly increased APP protein level and Aβ generation. Moreover, the increase of
APP level was not resulted from the enhancement APP gene transcription but due to the
inhibition of APP protein degradation. This work indicated that hyperglycemia could promote
AD development by increasing APP expression and facilitating APP processing and Aβ
production, suggesting glycemic control might be beneficial for AD treatment.Medicine, Faculty ofGraduat