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探索利用分子检测法和动物模型进行阿尔茨海默病早期检测的进展。

Exploring advancements in early detection of Alzheimer's disease with molecular assays and animal models.

机构信息

GloNeuro, Sector 107, Vishwakarma Road, Noida, Uttar Pradesh 201301, India.

School of Chemical Engineering, Yeungnam University, Gyeonsang 38541, Republic of Korea; Research Institute of Cell Culture, Yeungnam University, Gyeonsang 38541, Republic of Korea.

出版信息

Ageing Res Rev. 2024 Sep;100:102411. doi: 10.1016/j.arr.2024.102411. Epub 2024 Jul 8.

DOI:10.1016/j.arr.2024.102411
PMID:38986845
Abstract

Alzheimer's Disease (AD) is a challenging neurodegenerative condition, with overwhelming implications for affected individuals and healthcare systems worldwide. Animal models have played a crucial role in studying AD pathogenesis and testing therapeutic interventions. Remarkably, studies on the genetic factors affecting AD risk, such as APOE and TREM2, have provided valuable insights into disease mechanisms. Early diagnosis has emerged as a crucial factor in effective AD management, as demonstrated by clinical studies emphasizing the benefits of initiating treatment at early stages. Novel diagnostic technologies, including RNA sequencing of microglia, offer promising avenues for early detection and monitoring of AD progression. Therapeutic strategies remain to evolve, with a focus on targeting amyloid beta (Aβ) and tau pathology. Advances in animal models, such as APP-KI mice, and the advancement of anti-Aβ drugs signify progress towards more effective treatments. Therapeutically, the focus has shifted towards intricate approaches targeting multiple pathological pathways simultaneously. Strategies aimed at reducing Aβ plaque accumulation, inhibiting tau hyperphosphorylation, and modulating neuroinflammation are actively being explored, both in preclinical models and clinical trials. While challenges continue in developing validated animal models and translating preclinical findings to clinical success, the continuing efforts in understanding AD at molecular, cellular, and clinical levels offer hope for improved management and eventual prevention of this devastating disease.

摘要

阿尔茨海默病(AD)是一种具有挑战性的神经退行性疾病,对全球受影响的个人和医疗保健系统都有巨大的影响。动物模型在研究 AD 发病机制和测试治疗干预方面发挥了至关重要的作用。值得注意的是,对影响 AD 风险的遗传因素(如 APOE 和 TREM2)的研究为疾病机制提供了有价值的见解。早期诊断已成为 AD 有效管理的关键因素,临床研究强调在早期阶段开始治疗的益处证明了这一点。新型诊断技术,包括小胶质细胞的 RNA 测序,为 AD 进展的早期检测和监测提供了有前途的途径。治疗策略仍在不断发展,重点是针对淀粉样蛋白β(Aβ)和 tau 病理学。动物模型的进展,如 APP-KI 小鼠,以及抗 Aβ 药物的进步,标志着朝着更有效治疗方法的进展。治疗上,重点已转向同时针对多个病理途径的复杂方法。目前正在积极探索旨在减少 Aβ 斑块积累、抑制 tau 过度磷酸化和调节神经炎症的策略,这些策略既在临床前模型中,也在临床试验中进行探索。虽然在开发经过验证的动物模型和将临床前发现转化为临床成功方面仍然存在挑战,但在分子、细胞和临床水平上不断努力理解 AD 为改善管理和最终预防这种破坏性疾病提供了希望。

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