整合性晚发型阿尔茨海默病（LOAD）易感基因：胆固醇代谢与转运视角

Integrated late onset Alzheimer's disease (LOAD) susceptibility genes: Cholesterol metabolism and trafficking perspectives.

作者信息

Dong Hee Kim, Gim Jeong-An, Yeo Seung Hyeon, Kim Heui-Soo

机构信息

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea; Department of Psychiatry, Hyungju Hospital, Yangsan-si, Gyeongsangnam-do, Republic of Korea.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea; Genetic Engineering Institute, Pusan National University, Busan 46241, Republic of Korea.

出版信息

Gene. 2017 Jan 15;597:10-16. doi: 10.1016/j.gene.2016.10.022. Epub 2016 Oct 20.

DOI:10.1016/j.gene.2016.10.022

PMID:27773727

Abstract

Late onset Alzheimer's disease (LOAD) is the most common type of dementia and is characterized by decreased amyloid-β (Aβ) clearance from the brain. Cholesterol regulates the production and clearance of Aβ. Genome-wide association study (GWAS) suggests that at least 20 genes are associated with LOAD. The genes APOE, CLU, SORL1, PICALM, and BIN1 have a relatively high LOAD susceptibility. Additional experimental and bioinformatic approaches to integrate data from genetics, epigenetics, and molecular networks may further increase our understanding of LOAD in relation to cholesterol metabolism and trafficking.

摘要

晚发性阿尔茨海默病（LOAD）是最常见的痴呆类型，其特征是大脑中β淀粉样蛋白（Aβ）清除减少。胆固醇调节Aβ的产生和清除。全基因组关联研究（GWAS）表明至少有20个基因与LOAD相关。载脂蛋白E（APOE）、簇集素（CLU）、sortilin相关受体1（SORL1）、磷脂酰肌醇结合网格蛋白装配蛋白（PICALM）和桥连整合器1（BIN1）基因具有相对较高的LOAD易感性。整合来自遗传学、表观遗传学和分子网络数据的其他实验和生物信息学方法，可能会进一步加深我们对LOAD与胆固醇代谢和运输关系的理解。