Titze-de-Almeida Simoneide Souza, Marina Clara Luna, Ramos Milena Vieira, Silva Letícia Dias Dos Santos, Brandão Pedro Renato de Paula, Bispo Diógenes Diego de Carvalho, Von Glehn Felipe, Titze-de-Almeida Ricardo
Research Center for Major Themes-Neurodegenerative Disorders Division, University of Brasília, Brasília 70910-900, Federal District, Brazil.
Faculdade de Medicina, University of Rio Verde, Aparecida de Goiânia 74923-590, Goiás, Brazil.
Int J Mol Sci. 2025 Aug 25;26(17):8246. doi: 10.3390/ijms26178246.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily characterized by memory loss and cognitive decline, which significantly impacts patients' quality of life and imposes substantial emotional, practical, and economic burdens on their families. As the most common cause of senile dementia, AD currently affects approximately 50 million people worldwide, with projections indicating a threefold increase by 2050 due to rising life expectancy and an aging global population. Diagnosis of AD remains challenging. Neuroimaging techniques reveal atrophy in critical brain regions, particularly in the cortex, hippocampus, and limbic system, which are essential substrates for memory, personality changes, and other cognitive functions. The hallmark molecular changes associated with AD include the accumulation of β-amyloid plaques and the formation of tau protein tangles. Several underlying mechanisms contribute to neuron loss, such as oxidative stress, neuroinflammation, microbial dysbiosis, and insulin resistance. In this context, exosomes-small extracellular vesicles that facilitate cell communication-transport proteins, DNA, mRNA, and non-coding RNA (ncRNA), all of which play a significant role in the neurobiology of AD. Furthermore, emerging research indicates that exosomal ncRNAs may serve as promising biomarkers for AD, offering the possibility of improved diagnostic precision. This review explores the potential of exosomal ncRNAs-specifically circular RNAs and microRNAS-as non-invasive biomarkers for AD, highlighting recent advances and future directions in translational studies.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，主要特征为记忆丧失和认知衰退，这严重影响患者的生活质量，并给其家庭带来巨大的情感、实际和经济负担。作为老年痴呆最常见的病因，AD目前在全球约影响5000万人，预计到2050年，由于预期寿命延长和全球人口老龄化，这一数字将增至三倍。AD的诊断仍然具有挑战性。神经成像技术显示关键脑区出现萎缩，尤其是在皮层、海马体和边缘系统，这些区域是记忆、人格改变和其他认知功能的重要基础。与AD相关的标志性分子变化包括β-淀粉样蛋白斑块的积累和tau蛋白缠结的形成。几种潜在机制导致神经元丢失，如氧化应激、神经炎症、微生物群落失调和胰岛素抵抗。在此背景下，外泌体——促进细胞通讯的小细胞外囊泡——可运输蛋白质、DNA、mRNA和非编码RNA（ncRNA），所有这些在AD的神经生物学中都发挥着重要作用。此外，新出现的研究表明，外泌体ncRNA可能是AD有前景的生物标志物，为提高诊断准确性提供了可能。本综述探讨了外泌体ncRNA——特别是环状RNA和微小RNA——作为AD非侵入性生物标志物的潜力，突出了转化研究的最新进展和未来方向。
