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Background:The British precursor protein (BRI2) influences amyloid precursor protein metabolism. Results: BRI2 lowers ␤-amyloid peptide levels by increasing levels of secreted insulin-degrading enzyme (IDE) in both cells and mice. Conclusion: BRI2 as a receptor protein regulates IDE levels and in turn promotes ␤-amyloid degradation. Significance: Targeting the regulation of IDE may lead to new approaches to therapeutically address sporadic Alzheimer disease.