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阿尔茨海默病:探索认知衰退的全貌。

Alzheimer's Disease: Exploring the Landscape of Cognitive Decline.

机构信息

CAS, a division of the American Chemical Society, Columbus Ohio 43210, United States.

出版信息

ACS Chem Neurosci. 2024 Nov 6;15(21):3800-3827. doi: 10.1021/acschemneuro.4c00339. Epub 2024 Oct 11.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. The pathology of AD is marked by the accumulation of amyloid beta plaques and tau protein tangles in the brain, along with neuroinflammation and synaptic dysfunction. Genetic factors, such as mutations in APP, PSEN1, and PSEN2 genes, as well as the APOE ε4 allele, contribute to increased risk of acquiring AD. Currently available treatments provide symptomatic relief but do not halt disease progression. Research efforts are focused on developing disease-modifying therapies that target the underlying pathological mechanisms of AD. Advances in identification and validation of reliable biomarkers for AD hold great promise for enhancing early diagnosis, monitoring disease progression, and assessing treatment response in clinical practice in effort to alleviate the burden of this devastating disease. In this paper, we analyze data from the CAS Content Collection to summarize the research progress in Alzheimer's disease. We examine the publication landscape in effort to provide insights into current knowledge advances and developments. We also review the most discussed and emerging concepts and assess the strategies to combat the disease. We explore the genetic risk factors, pharmacological targets, and comorbid diseases. Finally, we inspect clinical applications of products against AD with their development pipelines and efforts for drug repurposing. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding AD, to outline challenges, and to evaluate growth opportunities to further efforts in combating the disease.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是认知能力下降、记忆力减退和日常功能受损。AD 的病理学表现为大脑中淀粉样β斑块和tau 蛋白缠结的积累,以及神经炎症和突触功能障碍。遗传因素,如 APP、PSEN1 和 PSEN2 基因突变以及 APOE ε4 等位基因,会增加患 AD 的风险。目前可用的治疗方法仅能提供症状缓解,而不能阻止疾病进展。研究工作集中在开发针对 AD 潜在病理机制的疾病修饰疗法。用于 AD 的可靠生物标志物的鉴定和验证方面的进展为增强临床实践中的早期诊断、监测疾病进展和评估治疗反应提供了巨大的希望,以减轻这种破坏性疾病的负担。在本文中,我们分析了 CAS Content Collection 中的数据,以总结 AD 的研究进展。我们研究了发表情况,以期深入了解当前知识的进展和发展。我们还回顾了讨论最多和新兴的概念,并评估了对抗疾病的策略。我们探讨了遗传风险因素、药物靶点和合并症。最后,我们检查了针对 AD 的产品的临床应用及其开发管道和药物再利用的努力。本综述的目的是提供 AD 相关当前知识不断发展的全景图,概述挑战,并评估增长机会,以进一步努力对抗疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/11587518/1904dfc965f1/cn4c00339_0001.jpg

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