Jin Gong, Shaoqi Li, Xiaodong Han, Pin Wang, Wenxian Sun, Chang Xu, Heya Luan, Boye Wen, Jinxuan Guo, Cuibai Wei
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Nevertheless, the influence of autoantibodies in AD is marked by substantial heterogeneity, they may either mitigate disease progression by clearing pathogenic protein aggregates or exacerbate the pathological process through mechanisms such as the activation of inflammatory responses or the induction of neuronal damage.ObjectiveThis review aims to synthesize the various roles of autoantibodies in AD, examine the factors that influence their functions, and assess their potential application in precision immunotherapy.MethodsPubMed and Web of Science databases were searched for English-language papers (2015-2025). Peer-reviewed human, animal and cell studies, systematic reviews and meta-analyses were screened independently by two reviewers.ResultsA total of 87 studies were selected for inclusion, spanning human, animal, and cellular research. The findings indicated that certain autoantibodies, such as those targeting amyloid-β, tau, or 4-hydroxynonenal, may confer neuroprotective effects. Conversely, other autoantibodies, including those against BACE1, aquaporin-4, or HuD, may exacerbate AD pathology. Importantly, some autoantibodies were found to exhibit dual roles, contingent upon their specific modifications or the context of the disease.ConclusionsAutoantibodies constitute a double-edged immune axis in AD. Their impact hinges on antigen class, disease stage, isotype affinity and glycosylation. Precision strategies-like CAAR-T cell therapy, glycosylation modulation, and affinity optimization-offer therapeutic promise but require further validation.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251350292"},"PeriodicalIF":3.1000,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Autoantibodies in Alzheimer's disease: Multifaceted roles and therapeutic horizons.\",\"authors\":\"Jin Gong, Shaoqi Li, Xiaodong Han, Pin Wang, Wenxian Sun, Chang Xu, Heya Luan, Boye Wen, Jinxuan Guo, Cuibai Wei\",\"doi\":\"10.1177/13872877251350292\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by pathogenesis involving numerous factors. Recent research has highlighted the significant role of autoimmunity in the initiation and progression of AD, with autoantibodies emerging as a pivotal area of investigation. Nevertheless, the influence of autoantibodies in AD is marked by substantial heterogeneity, they may either mitigate disease progression by clearing pathogenic protein aggregates or exacerbate the pathological process through mechanisms such as the activation of inflammatory responses or the induction of neuronal damage.ObjectiveThis review aims to synthesize the various roles of autoantibodies in AD, examine the factors that influence their functions, and assess their potential application in precision immunotherapy.MethodsPubMed and Web of Science databases were searched for English-language papers (2015-2025). Peer-reviewed human, animal and cell studies, systematic reviews and meta-analyses were screened independently by two reviewers.ResultsA total of 87 studies were selected for inclusion, spanning human, animal, and cellular research. The findings indicated that certain autoantibodies, such as those targeting amyloid-β, tau, or 4-hydroxynonenal, may confer neuroprotective effects. Conversely, other autoantibodies, including those against BACE1, aquaporin-4, or HuD, may exacerbate AD pathology. Importantly, some autoantibodies were found to exhibit dual roles, contingent upon their specific modifications or the context of the disease.ConclusionsAutoantibodies constitute a double-edged immune axis in AD. Their impact hinges on antigen class, disease stage, isotype affinity and glycosylation. Precision strategies-like CAAR-T cell therapy, glycosylation modulation, and affinity optimization-offer therapeutic promise but require further validation.</p>\",\"PeriodicalId\":14929,\"journal\":{\"name\":\"Journal of Alzheimer's Disease\",\"volume\":\" \",\"pages\":\"13872877251350292\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-06-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Alzheimer's Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/13872877251350292\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Alzheimer's Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/13872877251350292","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
阿尔茨海默病(AD)是一种神经退行性疾病,其发病机制涉及多种因素。最近的研究强调了自身免疫在阿尔茨海默病的发生和发展中的重要作用,自身抗体成为研究的关键领域。然而,自身抗体对阿尔茨海默病的影响具有很大的异质性,它们可能通过清除致病蛋白聚集体来减缓疾病进展,也可能通过激活炎症反应或诱导神经元损伤等机制加剧病理过程。目的综述自身抗体在阿尔茨海默病中的各种作用,探讨影响其功能的因素,并评价其在精密免疫治疗中的应用潜力。方法检索spubmed和Web of Science数据库2015-2025年的英文论文。同行评议的人类、动物和细胞研究、系统评价和荟萃分析由两位审稿人独立筛选。结果共纳入87项研究,涵盖人类、动物和细胞研究。研究结果表明,某些自身抗体,如靶向淀粉样蛋白-β、tau或4-羟基壬烯醛的抗体,可能具有神经保护作用。相反,其他自身抗体,包括针对BACE1、水通道蛋白-4或HuD的抗体,可能会加重AD的病理。重要的是,一些自身抗体被发现表现出双重作用,这取决于它们的特定修饰或疾病的背景。结论自身抗体在阿尔茨海默病中构成双刃剑免疫轴。它们的影响取决于抗原类别、疾病分期、同型亲和力和糖基化。精确的策略,如car - t细胞治疗、糖基化调节和亲和力优化,提供了治疗的希望,但需要进一步的验证。
Autoantibodies in Alzheimer's disease: Multifaceted roles and therapeutic horizons.
BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by pathogenesis involving numerous factors. Recent research has highlighted the significant role of autoimmunity in the initiation and progression of AD, with autoantibodies emerging as a pivotal area of investigation. Nevertheless, the influence of autoantibodies in AD is marked by substantial heterogeneity, they may either mitigate disease progression by clearing pathogenic protein aggregates or exacerbate the pathological process through mechanisms such as the activation of inflammatory responses or the induction of neuronal damage.ObjectiveThis review aims to synthesize the various roles of autoantibodies in AD, examine the factors that influence their functions, and assess their potential application in precision immunotherapy.MethodsPubMed and Web of Science databases were searched for English-language papers (2015-2025). Peer-reviewed human, animal and cell studies, systematic reviews and meta-analyses were screened independently by two reviewers.ResultsA total of 87 studies were selected for inclusion, spanning human, animal, and cellular research. The findings indicated that certain autoantibodies, such as those targeting amyloid-β, tau, or 4-hydroxynonenal, may confer neuroprotective effects. Conversely, other autoantibodies, including those against BACE1, aquaporin-4, or HuD, may exacerbate AD pathology. Importantly, some autoantibodies were found to exhibit dual roles, contingent upon their specific modifications or the context of the disease.ConclusionsAutoantibodies constitute a double-edged immune axis in AD. Their impact hinges on antigen class, disease stage, isotype affinity and glycosylation. Precision strategies-like CAAR-T cell therapy, glycosylation modulation, and affinity optimization-offer therapeutic promise but require further validation.
期刊介绍:
The Journal of Alzheimer''s Disease (JAD) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer''s disease. The journal publishes research reports, reviews, short communications, hypotheses, ethics reviews, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer''s disease.