International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 175-184 http://medscipublisher.com/index.php/ijmms 175 Case Study Open Access The Changes in Blood Exosomal miRNA Profiles and Disease Progression in Alzheimer’s Disease Patients Qiyan Lou, Xiaoying Xu Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: xiaoying.xu@cuixi.org International Journal of Molecular Medical Science, 2025, Vol.15, No.4 doi: 10.5376/ijmms.2025.15.0018 Received: 10 Jun., 2025 Accepted: 20 Jul., 2025 Published: 30 Jul., 2025 Copyright © 2025 Lou and Xu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Lou Q.Y., and Xu X.Y., 2025, The changes in blood exosomal miRNA Profiles and disease progression in alzheimer’s disease patients, International Journal of Molecular Medical Science, 15(4): 175-184 (doi: 10.5376/ijmms.2025.15.0018) Abstract This study reviews the current evidence on the differences in miRNA expression in exosomes of AD patients, highlighting several mirnas that have been repeatedly studied, such as miR-342-3p, miR-125b, miR-193b and miR-30b-5p. These mirnas are involved in the key pathological processes of AD, including brain inflammation, nerve cell death and synaptic function problems, and their expression levels change with the disease stage and are related to cognitive test scores and brain scan results. Research also indicates that these exosome mirnas may not only reflect the disease state but also directly participate in the development of the disease by influencing the information transmission between nerve cells and the gene regulatory network. Pathway analysis further linked these mirnas to pathways related to MAPK signaling, tgf-β signaling, and synaptic plasticity. The predictive model established using these miRNA combinations demonstrated a very high diagnostic accuracy (AUC>0.85). If combined with brain imaging and cognitive data, the predictive effect would be even better. Although the results are encouraging, for them to be truly applied in clinical practice, it is still necessary to unify the testing methods, verify the results in large-scale multi-center studies, and have a deeper understanding of their mechanism of action. Exosome mirnas have great potential in the early detection, disease tracking and individualized treatment of AD. Keywords Alzheimer’s disease; Exosomal microRNA; Biomarker; Neuroinflammation; Disease progression 1 Introduction Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. With the aging of the population, it is imposing an increasingly heavy burden on patients, families and the medical system. It is estimated that by 2050, the number of global AD patients will increase to approximately 50 million, which is three times the current number. The main manifestations of AD are memory loss, decreased thinking ability and loss of daily living skills, but there is still a lack of effective treatment methods at present. Early diagnosis is very difficult because brain lesions often begin several years before symptoms appear. Existing diagnostic methods, such as cerebrospinal fluid (CSF) examination and brain scans, are cumbersome to operate and costly, and are not suitable for large-scale population screening (Jain et al., 2019; Wang et al., 2023). Exosomes are tiny vesicles released by various cells, including nerve cells, and are present in body fluids such as blood. They carry proteins, lipids and nucleic acids, including a small RNA (called miRNA) that can regulate genes. Exosomal mirnas in the blood are very stable and can reflect the health or disease status of the source cells. Therefore, they are ideal targets for searching for markers of neurological diseases (Giau and An, 2016; Cui et al., 2021). Compared with healthy individuals, many studies have found that the expression of exosomal mirnas in the blood of AD patients is different. Some of these mirnas (such as miR-342-3p, miR-125b, miR-30b-5p, miR-193b) have been repeatedly proposed as potential diagnostic or disease prediction markers (Manna et al., 2020; Dong et al., 2021). These miRNA combinations not only have good diagnostic accuracy, but may also help us understand the pathogenesis and disease progression of AD (Cheng et al., 2014; Lugli et al., 2015; Yang et al., 2018; Jain et al., 2019; Nagaraj et al., 2019). This study will explore the shortcomings of current diagnostic methods and emphasize the urgent need for a convenient and reliable non-invasive biomarker to achieve early detection and disease monitoring of AD. Blood-based exosomal mirnas offer a minimally invasive, repeatable and suitable alternative for large-scale
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