摘要
APOE-ε4是最强的阿尔茨海默病(AD)的遗传风险因素,并与增加水平相关的淀粉样蛋白沉积和早期发病的年龄相关。最近的数据表明AD病理变化出现在临床症状前几十年,我们开始疑问具体疾病的发作。现在的在小鼠和人类身上的融合方法证明,APOE-ε4影响正常的大脑功能,虽然早期生活中没有病理变化。正常小鼠表达APOE4有特定任务的空间,以及减少NMDAR-dependent信号和结构性变化在神经元突触前和突触后区域,尤其是海马区域。年轻人拥有的APOE-ε4比APOE-ε4更善于一些行为的测试,功能性磁共振成像表明,继承APOE-ε4的具体影响内侧颞脑活动。这些发现表明,APOE-ε4的遗传引起大脑终身的变化,可能与后期AD的有关。几个可能的APOE-ε4机制会如何影响大脑神经化学、结构和功能进行了综述。
关键词: 载脂蛋白E、淀粉、内嗅皮层、树突棘、海马体、目标替代老鼠、预防、风险因素。
Current Alzheimer Research
Title:Alzheimer’s Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function
Volume: 13 Issue: 11
Author(s): Amanda M. Di Battista, Nicolette M. Heinsinger, G. William Rebeck
Affiliation:
关键词: 载脂蛋白E、淀粉、内嗅皮层、树突棘、海马体、目标替代老鼠、预防、风险因素。
摘要: APOE-ε4 is the strongest genetic risk factor for Alzheimer’s disease (AD), and is associated with an increase in the levels of amyloid deposition and an early age of onset. Recent data demonstrate that AD pathological changes occur decades before clinical symptoms, raising questions about the precise onset of the disease. Now a convergence of approaches in mice and humans has demonstrated that APOE-ε4 affects normal brain function even very early in life in the absence of gross AD pathological changes. Normal mice expressing APOE4 have task-specific spatial learning deficits, as well as reduced NMDAR-dependent signaling and structural changes to presynaptic and postsynaptic compartments in neurons, particularly in hippocampal regions. Young humans possessing APOE-ε4 are more adept than APOE-ε4 negative individuals at some behavioral tasks, and functional magnetic resonance imaging has shown that inheritance of APOE-ε4 has specific effects on medial temporal brain activities. These findings suggest that inheritance of APOE-ε4 causes life long changes to the brain that may be related to the late risk of AD. Several possible mechanisms of how APOE-ε4 could affect brain neurochemistry, structure, and function are reviewed.
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Cite this article as:
Amanda M. Di Battista, Nicolette M. Heinsinger, G. William Rebeck , Alzheimer’s Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function, Current Alzheimer Research 2016; 13 (11) . https://dx.doi.org/10.2174/1567205013666160401115127
DOI https://dx.doi.org/10.2174/1567205013666160401115127 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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