{"title":"Apolipoprotein E in Alzheimer's Disease: Focus on Synaptic Function and Therapeutic Strategy.","authors":"Longjie Qu, Shuai Xu, Zhen Lan, Shuang Fang, Yun Xu, Xiaolei Zhu","doi":"10.1007/s12035-024-04449-1","DOIUrl":null,"url":null,"abstract":"<p><p>Synaptic dysfunction is a critical pathological feature in the early phase of Alzheimer's disease (AD) that precedes typical hallmarks of AD, including beta-amyloid (Aβ) plaques and neurofibrillary tangles. However, the underlying mechanism of synaptic dysfunction remains incompletely defined. Apolipoprotein E (APOE) has been shown to play a key role in the pathogenesis of AD, and the ε4 allele of APOE remains the strongest genetic risk factor for sporadic AD. It is widely recognized that APOE4 accelerates the development of Aβ and tau pathology in AD. Recent studies have indicated that APOE affects synaptic function through a variety of pathways. Here, we summarize the mechanism of modulating synapses by various APOE isoforms and demonstrate the therapeutic potential by targeting APOE4 for AD treatment.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3040-3052"},"PeriodicalIF":4.6000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12035-024-04449-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/31 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Synaptic dysfunction is a critical pathological feature in the early phase of Alzheimer's disease (AD) that precedes typical hallmarks of AD, including beta-amyloid (Aβ) plaques and neurofibrillary tangles. However, the underlying mechanism of synaptic dysfunction remains incompletely defined. Apolipoprotein E (APOE) has been shown to play a key role in the pathogenesis of AD, and the ε4 allele of APOE remains the strongest genetic risk factor for sporadic AD. It is widely recognized that APOE4 accelerates the development of Aβ and tau pathology in AD. Recent studies have indicated that APOE affects synaptic function through a variety of pathways. Here, we summarize the mechanism of modulating synapses by various APOE isoforms and demonstrate the therapeutic potential by targeting APOE4 for AD treatment.
突触功能障碍是阿尔茨海默病（AD）早期的一个关键病理特征，它先于AD的典型特征，包括β-淀粉样蛋白（Aβ）斑块和神经纤维缠结。然而，突触功能障碍的内在机制仍未完全明确。载脂蛋白E（APOE）已被证明在AD的发病机制中起着关键作用，而APOE的ε4等位基因仍是散发性AD最强的遗传风险因素。人们普遍认为，APOE4 会加速 AD 中 Aβ 和 tau 病理学的发展。最近的研究表明，APOE 通过多种途径影响突触功能。在此，我们总结了各种APOE异构体调节突触的机制，并展示了针对APOE4治疗AD的治疗潜力。
期刊介绍：
Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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