The APOE4 protein affects the primary neuropathological markers of Alzheimer's disease (AD): amyloid plaques, neurofibrillary tangles, and gliosis. These interactions have been investigated to understand the strong effect of APOE genotype on risk of AD. However, APOE genotype has strong effects on processes in normal brains, in the absence of the hallmarks of AD. We propose that CNS APOE is involved in processes in the normal brains that in later years apply specifically to processes of AD pathogenesis. We review the differences of the APOE protein found in the CNS compared to the plasma, including post-translational modifications (glycosylation, lipidation, multimer formation), focusing on ways that the common APOE isoforms differ from each other. We also review structural and functional studies of young human brains and control APOE knock-in mouse brains. These approaches demonstrate the effects of APOE genotype on microscopic neuron structure, gross brain structure, and behavior, primarily related to the hippocampal areas. By focusing on the effects of APOE genotype on normal brain function, approaches can be pursued to identify biomarkers of APOE dysfunction, to promote normal functions of the APOE4 isoform, and to prevent the accumulation of the pathologic hallmarks of AD with aging.

中文翻译：

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正常大脑中的APOE。

APOE4蛋白会影响阿尔茨海默氏病（AD）的主要神经病理学标志：淀粉样斑块，神经原纤维缠结和神经胶质增生。已对这些相互作用进行了调查，以了解APOE基因型对AD风险的强大影响。但是，在没有AD的特征的情况下，APOE基因型对正常大脑的过程有很强的影响。我们建议中枢神经系统APOE参与正常脑中的过程，在以后的几年中专门应用于AD发病机理。我们回顾了中枢神经系统与血浆相比发现的APOE蛋白的差异，包括翻译后修饰（糖基化，脂质化，多聚体形成），重点介绍了常见APOE同工型彼此不同的方式。我们还审查了年轻人的大脑和控制APOE敲入小鼠大脑的结构和功能研究。这些方法证明了APOE基因型对主要与海马区有关的微观神经元结构，总体脑结构和行为的影响。通过关注APOE基因型对正常脑功能的影响，可以寻求方法来识别APOE功能障碍的生物标志物，促进APOE4亚型的正常功能并防止衰老引起AD病理学标志的积累。