Abstract
In Alzheimer disease, a combination of genetic predisposition and environmental factors may contribute to changes in beta-amyloid precursor protein (APP) expression, beta-amyloid peptide deposition, and neuronal loss. Factors such as head injury or acute infection that trigger inflammatory processes may play a crucial role in development of the disease. In the present in vivo study, we showed that, in mouse brain, peripheral stimulation with lipopolysaccharide (LPS) induced a transient increase in the inflammatory cytokine mRNAs (interleukin 1 beta and interleukin 6), followed by changes in expression of APP isoforms in the cerebellum but not in the cerebral cortex. These changes consisted of a decrease in the APP-695 and an increase in the Kunitz protease inhibitor-bearing isoforms (KPI-APP). In the cerebellum of the staggerer mouse mutant, where a severe loss of Purkinje and granule cells occurs, basal mRNA levels of these interleukins were elevated and an increase in the KPI-APP/APP-695 ratio compared to wild-type mice was observed. These abnormalities were further accentuated by LPS stimulation. This study shows that acute and chronic inflammatory processes play an important role in changes in APP expression possibly associated with neurodegeneration.