Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Br J Biomed Sci. 2024 Oct 7;81:13169. doi: 10.3389/bjbs.2024.13169. eCollection 2024.
This review delves into the entorhinal cortex (EC) as a central player in the pathogenesis of Alzheimer's Disease (AD), emphasizing its role in the accumulation and propagation of tau pathology. It elucidates the multifaceted functions of the EC, encompassing memory formation, spatial navigation, and olfactory processing, while exploring how disruptions in these processes contribute to cognitive decline in AD. The review discusses the intricate interplay between tau pathology and EC vulnerability, highlighting how alterations in neuronal firing patterns and synaptic function within the EC exacerbate cognitive impairments. Furthermore, it elucidates how specific neuronal subtypes within the EC exhibit differential susceptibility to tau-induced damage, contributing to disease progression. Early detection methods, such as imaging techniques and assessments of EC blood flow, are examined as potential tools for identifying tau pathology in the preclinical stages of AD. These approaches offer promise for improving diagnostic accuracy and enabling timely intervention. Therapeutic strategies targeting tau pathology within the EC are explored, including the clearance of pathological tau aggregates and the inhibition of tau aggregation processes. By understanding the molecular and cellular mechanisms underlying EC vulnerability, researchers can develop more targeted and effective interventions to slow disease progression. The review underscores the importance of reliable biomarkers to assess disease progression and therapeutic efficacy in clinical trials targeting the EC. Ultimately, it aims to contribute to the development of more effective management strategies for AD, emphasizing the translation of research findings into clinical practice to address the growing societal burden of the disease.
这篇综述深入探讨了内嗅皮层(EC)在阿尔茨海默病(AD)发病机制中的核心作用,强调了其在tau 病理学积累和传播中的作用。它阐明了 EC 的多方面功能,包括记忆形成、空间导航和嗅觉处理,同时探讨了这些过程的紊乱如何导致 AD 中的认知能力下降。该综述讨论了 tau 病理学与 EC 易损性之间的复杂相互作用,强调了 EC 内神经元放电模式和突触功能的改变如何加剧认知障碍。此外,它阐明了 EC 内特定神经元亚型对 tau 诱导损伤的不同易感性如何导致疾病进展。还检查了 EC 血流评估等早期检测方法作为在 AD 的临床前阶段识别 tau 病理学的潜在工具。这些方法有望提高诊断准确性并实现及时干预。还探讨了针对 EC 内 tau 病理学的治疗策略,包括清除病理性 tau 聚集体和抑制 tau 聚集过程。通过了解 EC 易损性的分子和细胞机制,研究人员可以开发更有针对性和有效的干预措施来减缓疾病进展。该综述强调了可靠生物标志物的重要性,以评估针对 EC 的临床试验中的疾病进展和治疗效果。最终,它旨在为 AD 的更有效管理策略做出贡献,强调将研究结果转化为临床实践,以应对疾病日益增长的社会负担。