阿尔茨海默病
发病机制
医学
神经退行性变
海马体
神经炎症
血脑屏障
ABCA1
海马结构
内分泌学
内科学
痴呆
转基因小鼠
早老素
老年斑
作者
Woojin Jeong,Hyein Lee,Sukhee Cho,Jinsoo Seo
出处
期刊:Molecules and Cells
[Korean Society for Molecular and Cellular Biology]
日期:2019-11-30
卷期号:42 (11): 739-746
被引量:23
标识
DOI:10.14348/molcells.2019.0200
摘要
Significant knowledge about the pathophysiology of Alzheimer's disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.
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