Objective To investigate the effects of nutritional intervention on brain insulin degrading enzyme ( IDE) and neprilysin(NEP) levels in APP⁃PSN transgenic mice with Alzheimer�s disease(AD), and to study the mechanism of combined nutrients on prevention and remission for AD. Methods Seventy⁃two APP⁃PSN transgenic mice aged two months were randomly divided into the intervention group supplied with compound recipe in the diet and the model group fed with basic feed, and the intervention group were divided into high⁃and low⁃dose group. Another 24 APP⁃PSN transgenic negative mice were selected as negative control group. After intervention for 7 months, immunohistochemistry staining was used to evaluate the pathology in brain, and the levels of IDE and NEP in mice brain were detected by ELISA. Results By immunohistochemical staining with antibody against beta Amyloid1⁃42 ( Aβ1⁃42 ) , hippocampus and cerebral cortex in model group mice appeared more typical flaxen plaque deposition (+++) , and high⁃and low⁃dose group showed less pale yellow plaque deposition (+) , and plaque deposits was not found in negative control group (-) . Compared with model group, the levels of IDE and NEP in high⁃and low⁃dose groups showed significant difference( P<0�05) . Conclusions Compound nutrition intervention may improve AD,through improving the activity and levels of IDE and NEP in APP⁃PSN double transgenic mice and delaying the deposition of amyloid plaques in the cerebral cortex and the hippocampus of APP⁃PSN mice.%目的采用复合营养素对阿尔茨海默病（ AD） APP⁃PSN双转基因小鼠营养干预，观察脑内胰岛素降解酶（IDE）和脑啡肽酶（NEP）水平的差异，探讨营养干预对AD预防和缓解的作用机制。方法将72只2月龄APP⁃PSN双转基因小鼠，随机分为干预组和模型组，干预组又分高、低2个剂量组；24只APP⁃PSN转基因阴性小鼠作为阴性对照组。干预组饲喂添加复合营养素的饲料，模型组和阴性对照组饲喂基础饲料。在干预7月后，免疫组织化学法染色观察小鼠脑组织中老年斑沉积；采用酶联免疫吸附试验方法检测各组小鼠脑组织内IDE和NEP水平。结果模型组小鼠大脑皮层及海马区有较多β淀粉样淡黄色斑块沉积（＋＋＋）；高、低干预组分布较少（＋）；阴性对照组无沉积（－）。小鼠脑内IDE和NEP水平，高、低干预组与模型组均有统计学差异（ P＜0�05）。结论复合营养素干预能够提高APP⁃PSN双转基因小鼠脑内IDE及NEP 的活性及含量，减少β淀粉样蛋白沉积，有改善AD病情，预防AD的作用。
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