Brain A accumulation represents a key pathological hallmark in Alzheimers disease.

In this study, we investigated the impact of anata ine, a minor alkaloid presen t in plants of the Solanacea family on A production in vitro using a cell line ov erexpressing the human amyloid precursor protein (APP) and in vivo using a trans genic mouse model of Alzheimers disease. In vitro, anata ine lowers A and A leve e dependent manner and reduces sAPP production without impacting sAPP levels sugge sting th t n t bine lowers A production y mainly impacting the -cleavage of APP. Additionally, we show that anata ine lowers NFB ctiv tion t doses th t inhibit A production in vitro. Since NFB is nown to regul te BACE-1 expression (the r te limiting enzyme responsible for A production), we determined the impact of anata ine on BACE-1 transcription. We show that anata ine inhi its BACE-1 transcripti on and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells sugges ting that the A lowering properties of anata ine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anata ine for four days significantly lowers rain solu le A and A levels in a transgenic mouse Alzheimers disease. Altogether our data suggest that anata ine may represent an interesting compound for regulating rain A accumulation.

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