Islam Sadequl, Noorani Arshad, Sun Yang, Michikawa Makoto, Zou Kun
Department of Neuro-Oncology, Graduate School of Medical Sciences, Institute of Brain Science, Nagoya City University, Nagoya, Japan.
Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, United States.
Front Aging Neurosci. 2025 Jan 29;17:1535280. doi: 10.3389/fnagi.2025.1535280. eCollection 2025.
Genetic diversity in the apolipoprotein E (ApoE) gene has been identified as the major susceptibility genetic risk factor for sporadic Alzheimer's disease (SAD). Specifically, the allele is a significant risk factor for SAD, while allele provides protection compared to the more common allele. This review discusses the role of the ApoE in AD and other neurodegenerative disorders. ApoE, a cholesterol transport protein, influences several pathways involved in neurodegeneration, particularly in AD. Beyond its established role in amyloid -protein (Aβ) metabolism and deposition, ApoE also impacts tau pathology, neurodegeneration, and the microglial response to AD. The review aims to provide an updated overview of ApoE's diverse roles, emphasizing its involvement in Aβ clearance through ApoE receptors. It also covers ApoE's influence in other neurodegenerative diseases like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington's disease (HD), vascular dementia (VD), and multiple sclerosis (MS). New research highlights the interaction between ApoE and presenilin (PS), suggesting connections between familial AD (FAD) and SAD. The review also explores protective effects of ApoE mutations against AD and ApoE4-induced tauopathy, neurodegeneration, and neuroinflammation. The insights from this comprehensive update could indeed lead to new therapeutic strategies for neurodegenerative diseases.
载脂蛋白E（ApoE）基因的遗传多样性已被确定为散发性阿尔茨海默病（SAD）的主要易感性遗传风险因素。具体而言， 等位基因是SAD的重要风险因素，而与更常见的 等位基因相比， 等位基因具有保护作用。本综述讨论了ApoE在阿尔茨海默病和其他神经退行性疾病中的作用。ApoE是一种胆固醇转运蛋白，影响神经退行性变相关的多种途径，尤其是在阿尔茨海默病中。除了在淀粉样蛋白（Aβ）代谢和沉积中已确定的作用外，ApoE还影响tau病理、神经退行性变以及小胶质细胞对阿尔茨海默病的反应。本综述旨在提供ApoE多种作用的最新概述，强调其通过ApoE受体参与Aβ清除。它还涵盖了ApoE在其他神经退行性疾病中的影响，如帕金森病（PD）、肌萎缩侧索硬化症（ALS）、额颞叶痴呆（FTLD）、亨廷顿舞蹈病（HD）、血管性痴呆（VD）和多发性硬化症（MS）。新的研究突出了ApoE与早老素（PS）之间的相互作用，提示家族性阿尔茨海默病（FAD）和SAD之间的联系。本综述还探讨了ApoE突变对阿尔茨海默病的保护作用以及ApoE4诱导的tau病变、神经退行性变和神经炎症。这一全面更新的见解确实可能带来神经退行性疾病的新治疗策略。
