International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 175-184 http://medscipublisher.com/index.php/ijmms 176 screening. The stability of miRNA in the blood and its disease-related expression patterns support its value as an early marker, which is expected to help with early treatment, improve the grouping of drug trials, and enhance therapeutic effects. 2 The Mechanism of Action of Exosomal miRNA in the Blood in Alzheimer's Disease 2.1 The function of exosomes in the communication between nerve cells Exosomes are tiny vesicles (nanometers in size) released by nerve cells and glial cells, capable of transporting substances such as proteins, lipids, mRNA and miRNA. This kind of "communication" between cells is very important for maintaining the balance within the brain and regulating the activity of neural signals. In Alzheimer's disease (AD), exosomes may carry pathogenic proteins (such as amyloid -β and tau proteins), which help these lesions spread in different regions of the brain (Giau and An, 2016; Chen et al., 2017; Manna et al., 2020; Wang and Zhang, 2020). In addition to delivering proteins, exosomes can also transport regulatory Rnas including mirnas, which can alter gene expression in nerve cells that receive information. This process regulates neural function and plasticity and may be involved in both maintaining normal brain activity and the transmission of disease signals in AD (Giau and An, 2016; Chen et al., 2017; Manna et al., 2020; Wang and Zhang, 2020). 2.2 miRNA regulates brain inflammation, cell death and neural plasticity Exosomal miRNA is a key molecule regulating gene expression and affects the core pathological process of AD. They can regulate brain inflammation, such as influencing the activation of microglia (the immune cells of the brain) and the production of inflammatory factors. Certain specific mirnas (such as miR-146a and miR-223-3p) are directly associated with inflammatory signaling pathways (Wang and Zhang, 2020; Kaur et al., 2023; Dong et al., 2024). If these mirnas are out of balance, they will intensify the inflammatory response and damage nerve cells. In addition, exosomal mirnas also regulate nerve cell death (apoptosis) and the plasticity of neural connections. For instance, miR-125b and miR-342-3p are involved in controlling the survival of nerve cells and synaptic function. Changes in their levels in AD patients are associated with increased nerve cell death and impaired neural signaling pathways (Lugli et al., 2015; Manna et al., 2020; Wang and Zhang, 2020; Wang et al., 2023). These regulatory effects demonstrate the significance of exosomal mirnas in the pathogenesis and progression of AD. 2.3 The significance of exosomal miRNA changes as an indicator of disease progression The miRNA profile of exosomes in the blood of AD patients will change, and the degree of certain specific miRNA changes is closely related to the severity of the disease and the decline in cognitive ability. For instance, decreased levels of exosomal miR-342-3p and miR-125b have been shown to be associated with clinical indicators of AD exacerbation (Lugli et al., 2015; Manna et al., 2020; Wang and Zhang, 2020; Wang et al., 2023). The changes in the miRNA levels of these exosomes not only reflect the intrinsic processes of the disease but also provide potential non-invasive markers for monitoring the progression of the condition. The detection combination composed of multiple abnormal mirnas demonstrated good diagnostic accuracy, which is conducive to the earlier detection of AD and better tracking of disease changes, supporting the value for clinical and research use (Lugli et al., 2015; Manna et al., 2020; Wang and Zhang, 2020; Dong et al., 2021; Song et al., 2021; Wang et al., 2023; Alhenaky et al., 2024; Duan et al., 2024). 3 The Clinical and Statistical Basis of The Research Population Grouping Design 3.1 AD staging and clinical feature criteria Accurately distinguishing the different stages of Alzheimer's disease (AD) is of great significance for both research and the search for biomarkers. AD staging usually combines clinical assessment, cognitive tests and biomarkers. For instance, based on an individual's cognitive ability, daily functional status, and abnormal conditions of amyloid and tau proteins shown by cerebrospinal fluid (CSF) or PET scans, it can be classified as: early disease (preclinical), mild memory impairment (MCI), or dementia stage (Insel et al., 2019; Xu et al., 2024).
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