The apolipoprotein E ɛ4 allele (APOE4) is universally acknowledged as the most potent genetic risk factor for Alzheimer's disease (AD). APOE4 promotes the initiation and progression of AD. Although the underlying mechanisms are unclearly understood, differences in lipid-bound affinity among the three APOE isoforms may constitute the basis. The protein APOE4 isoform has a high affinity with triglycerides and cholesterol. A distinction in lipid metabolism extensively impacts neurons, microglia, and astrocytes. APOE4 carriers exhibit phenotypic differences from non-carriers in clinical examinations and respond differently to multiple treatments. Therefore, we hypothesized that phenotypic classification of AD patients according to the status of APOE4 carrier will help specify research and promote its use in diagnosing and treating AD. Recent reviews have mainly evaluated the differences between APOE4 allele carriers and non-carriers from gene to protein structures, clinical features, neuroimaging, pathology, the neural network, and the response to various treatments, and have provided the feasibility of phenotypic group classification based on APOE4 carrier status. This review will facilitate the application of APOE phenomics concept in clinical practice and promote further medical research on AD.

中文翻译：

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基于载脂蛋白 E ɛ4 等位基因携带状态的阿尔茨海默病表型

载脂蛋白 E ɛ4等位基因 ( APOE4 ) 被普遍认为是阿尔茨海默病 (AD) 的最有效的遗传风险因素。APOE4促进 AD 的发生和进展。尽管根本机制尚不清楚，但三种 APOE 亚型之间脂质结合亲和力的差异可能构成基础。APOE4 蛋白亚型与甘油三酯和胆固醇具有高亲和力。脂质代谢的差异广泛影响神经元、小胶质细胞和星形胶质细胞。APOE4携带者在临床检查中表现出与非携带者的表型差异，并且对多种治疗的反应不同。因此，我们假设根据 APOE4 携带者的状态对 AD 患者进行表型分类将有助于规范研究并促进其在 AD 诊断和治疗中的应用。最近的综述主要评估了APOE4等位基因携带者与非携带者从基因到蛋白质结构、临床特征、神经影像、病理、神经网络以及对各种治疗的反应等方面的差异，并提供了基于APOE4等位基因的表型组分类的可行性。APOE4携带者状态。本综述将促进APOE表型组学概念在临床实践中的应用，并推动AD进一步的医学研究。