The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease
The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease
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DOI：
10.1038/ng1943
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发表时间：
2007-02-01
期刊：
影响因子：
30.8
通讯作者：
St George-Hyslop, Peter
中科院分区：
文献类型：
--
作者：
Rogaeva, Ekaterina;Meng, Yan;St George-Hyslop, Peter
淀粉样蛋白前体蛋白（APP）通过内吞途径从细胞表面再循环，在阿尔茨海默病中淀粉样蛋白β肽（a β）的生成中起关键作用。我们在此报告SORL1神经元分选受体的遗传变异与晚发性阿尔茨海默病有关。这些变异发生在SORL1基因（也称为LR11或SORLA）内至少两个不同的内含子序列簇中，可能调节SORL1的组织特异性表达。我们还表明SORL1指导APP的转运进入回收途径，当SORL1表达不足时，APP被分类到产生A β的区室中。这些数据表明，遗传或获得性SORL1表达或功能的改变在机制上参与了阿尔茨海默病的发生。
The recycling of the amyloid precursor protein ( APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide ( A beta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late- onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene ( also known as LR11 or SORLA) may regulate tissue- specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into A beta- generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.