Value of blood neural cell-derived small extracellular vesicles in the diagnosis and prediction of Alzheimer's disease: A systematic revie - 25/04/25
, Mingjing Zhao ⁎ 
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Highlights |
• | Blood neural cell-derived sEV Aβ- and tau-related proteins, synaptic proteins, and miRNAs are important biomarkers of AD. |
• | Blood neural cell-derived sEVs can predict the development of AD within 1-10 years. |
• | Compared with the existing blood diagnostic markers, the synaptic proteins in blood neural cell-derived sEVs show significant changes in the early clinical stage, which has the value of early diagnosis. |
• | Blood neural cell-derived sEVs, which are consistent with the changes of brain tissue, can not only detect pathological products related to AD, but also detect the changes of neurosynaptic proteins, and can better reflect the pathological changes of neurons than blood and CSF. |
• | Blood neural cell-derived sEVs have important clinical value for the diagnosis and early prediction of AD. |
Abstract |
Blood neural cell-derived small extracellular vesicles (sEVs) can directly reflect changes in brain tissue and are easier to obtain than cerebrospinal fluid. This article systematically reviews the alterations of proteins and miRNAs from neural cell-derived sEVs in patients with Alzheimer's disease (AD), and summarizes the biomarkers with clinical diagnostic and predictive value. PubMed, Web of Science, Embase, and Cochrane Library were searched for studies in blood neural cell-derived sEVs in AD patients up to May 2024. According to the inclusion and exclusion criteria, the literature was screened, the information was extracted and the quality was evaluated. Proteins and miRNAs from neural cell-derived sEVs were classified and summarized, focusing on target molecules with high diagnostic and predictive values for AD. A final 34 articles reporting 5601 participants were included. In cross-sectional studies, Aβ- and Tau-related proteins (Aβ42, Aβ42/40, p-S396-Tau, p-Tau181), p-S312-IRS-1, and cathepsin D were increased, conversely, synaptic proteins (neurogranin, synaptotagmin, synaptophysin, synaptopodin, NMDAR2A) and REST were decreased in blood neuron-derived sEVs (NDsEVs) of patients with AD. While miR-29c-3p was increased in blood NDsEVs and glial cell-derived sEVs. Each of these proteins and miRNAs demonstrated high AD diagnostic value. Additionally, blood astrocyte-derived sEVs (ADsEVs) showed increased complement effector proteins and decreased complement regulatory proteins with a moderate diagnostic value. In longitudinal cohort studies, three composite models displayed high predictive efficacy for early AD prediction, and could predict the occurrence of AD within 1-10 years. Therefore, Aβ- and Tau-related proteins, synaptic proteins, and miRNA in blood neural cell-derived sEVs demonstrate high AD diagnostic and predictive values serving as important biomarkers. Especially, synaptic proteins showed significant changes in the early clinical stage, which has early predictive value.
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KEYWORDS : blood neural cell-derived small extracellular vesicles, Alzheimer's disease, biomarker, diagnosis, prediction
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