{"title":"Structural and functional remodeling of neural networks in β-amyloid driven hippocampal hyperactivity","authors":"","doi":"10.1016/j.arr.2024.102468","DOIUrl":null,"url":null,"abstract":"<div><p>Early detection of Alzheimer’s disease (AD) is essential for improving the patients outcomes and advancing our understanding of disease, allowing for timely intervention and treatment. However, accurate biomarkers are still lacking. Recent evidence indicates that hippocampal hyperexcitability precedes the diagnosis of AD decades ago, can predict cognitive decline. Thus, could hippocampal hyperactivity be a robust biomarker for early-AD, and what drives hippocampal hyperactivity in early-AD? these critical questions remain to be answered. Increasing clinical and experimental studies suggest that early hippocampal activation is closely associated with longitudinal β-amyloid (Aβ) accumulation, Aβ aggregates, in turn, enhances hippocampal activity. Therefore, in this narrative review, we discuss the role of Aβ-induced altered intrinsic neuronal properties as well as structural and functional remodeling of glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic circuits in hippocampal hyperactivity. In addition, we analyze the available therapies and trials that can potentially be used clinically to attenuate hippocampal hyperexcitability in AD. Overall, the present review sheds lights on the mechanism behind Aβ-induced hippocampal hyperactivity, and highlights that hippocampal hyperactivity could be a robust biomarker and therapeutic target in prodromal AD.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":null,"pages":null},"PeriodicalIF":12.5000,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ageing Research Reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568163724002861","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Early detection of Alzheimer’s disease (AD) is essential for improving the patients outcomes and advancing our understanding of disease, allowing for timely intervention and treatment. However, accurate biomarkers are still lacking. Recent evidence indicates that hippocampal hyperexcitability precedes the diagnosis of AD decades ago, can predict cognitive decline. Thus, could hippocampal hyperactivity be a robust biomarker for early-AD, and what drives hippocampal hyperactivity in early-AD? these critical questions remain to be answered. Increasing clinical and experimental studies suggest that early hippocampal activation is closely associated with longitudinal β-amyloid (Aβ) accumulation, Aβ aggregates, in turn, enhances hippocampal activity. Therefore, in this narrative review, we discuss the role of Aβ-induced altered intrinsic neuronal properties as well as structural and functional remodeling of glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic circuits in hippocampal hyperactivity. In addition, we analyze the available therapies and trials that can potentially be used clinically to attenuate hippocampal hyperexcitability in AD. Overall, the present review sheds lights on the mechanism behind Aβ-induced hippocampal hyperactivity, and highlights that hippocampal hyperactivity could be a robust biomarker and therapeutic target in prodromal AD.
阿尔茨海默病(AD)的早期检测对于改善患者的预后和增进我们对疾病的了解,以便及时干预和治疗至关重要。然而,目前仍缺乏准确的生物标志物。最近的证据表明,海马过度兴奋性早在几十年前就已被诊断为阿兹海默症,并能预测认知能力的下降。因此,海马过度活跃能否成为早期AD的可靠生物标志物?越来越多的临床和实验研究表明,早期海马的激活与β淀粉样蛋白(Aβ)的纵向积累密切相关,而Aβ聚集反过来又会增强海马的活动。因此,在这篇叙述性综述中,我们讨论了 Aβ 引起的神经元内在特性改变以及谷氨酸能、GABAergic、胆碱能、去甲肾上腺素能、5-羟色胺能回路的结构和功能重塑在海马过度活跃中的作用。此外,我们还分析了现有的疗法和试验,这些疗法和试验有可能用于临床,以减轻 AD 的海马过度兴奋性。总之,本综述揭示了Aβ诱导海马过度活跃背后的机制,并强调海马过度活跃可能是AD前驱期的一个强有力的生物标志物和治疗靶点。
期刊介绍:
With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends.
ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research.
The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.