Neuronal Death, Proinflammatory Cytokines and Amyloid Precursor Protein: Studies on Staggerer Mutant Mice
In Alzheimer’s, disease (AD), a combination of genetic predisposition and environmental factors may contribute to changes in β-amyloid precursor protein (APP) expression, β-amyloid deposition and neuronal loss. Head injury and acute infection that triggers inflammatory processes are known to be risk factors. In the present in vivo study we show that peripheral endotoxin injection induces a phasic increase of IL-lβ and IL-6 mRNA in mouse cerebellum, followed within 24 hours by an increase in the APPKPI/APP-695 ratio. In the cerebellum of the staggerer mouse mutant, where a severe deficit of Purkinje and granule cells occurs, elevated basal levels of IL-lβ and IL-6 mRNA and an increase in the APP-KPI/APP-695 ratio compared to wild type mice was observed. LPS stimulation further accentuated these differences for cytokines and APP isoforms. Our in vivo studies suggest that interaction loops between cytokines and APP could play an important role in the regulation of APP expression in degenerating Alzheimer’s disease brain tissue.
KeywordsMigration Codon Agarose Dementia Penicillin
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