PDF(Pubmed)
Abstract：
Human APOE4 (apolipoprotein E4 isoform) is a powerful genetic risk factor for late-onset Alzheimer disease (AD). Many groups have investigated the effect of APOE4 on the degradation of amyloid β (Aβ), the main component of plaques found in the brains of AD patients. However, few studies have focused on the degradation of APOE itself. We investigated the lysosomal trafficking of APOE in cells and found that APOE from the post-Golgi compartment is degraded through an autophagic process requiring the lysosomal membrane protein LAMP2A. We found that APOE4 accumulates in enlarged lysosomes, alters autophagic flux, and changes the proteomic contents of lysosomes following internalization. This dysregulated lysosomal trafficking may represent one of the mechanisms that contributes to AD pathogenesis.
摘要：
人APOE4(载脂蛋白E4同工型)是迟发性阿尔茨海默病(AD)的强大遗传风险因子。许多研究小组已经研究了APOE4对淀粉样β（Aβ）降解的影响，在AD患者大脑中发现的斑块的主要成分。然而,很少有研究关注APOE本身的降解。我们研究了APOE在细胞中的溶酶体运输，发现高尔基后区室的APOE通过需要溶酶体膜蛋白LAMP2A的自噬过程降解。我们发现APOE4在扩大的溶酶体中积累，改变自噬通量，内化后改变溶酶体的蛋白质含量。这种失调的溶酶体运输可能代表促成AD发病机制之一。
