Dysregulated serum miR-384-5p as a diagnostic biomarker for Alzheimer’s disease

Abstract Objectives Alzheimer’s disease (AD) is classified as a neurodegenerative disorder. Studies have found that miR-384-5p plays a role in neurological diseases such as Parkinson’s. This study investigated the dysregulation of circulating miR-384-5p in Alzheimer’s disease patients through serum analysis. We investigated its diagnostic significance in AD, neuroprotective effects, and underlying mechanisms. Methods SH-SY5Y cells were treated with Aβ25-35 to model AD, and qRT-PCR quantified miR-384-5p expression in both serum and cellular components. The diagnostic potential of miR-384-5p for Alzheimer’s disease was evaluated through combined analysis of cognitive assessment (MMSE) and diagnostic accuracy validation (ROC curve). miR-384-5p demonstrated cytotoxic activity (MTT/flow cytometry) and target regulation (luciferase assay). Results miR-384-5p expression was significantly elevated in both AD patient serum and Aβ25-35-exposed SH-SY5Y cells (p<0.001). A significant inverse correlation was observed between miR-384-5p expression levels and MMSE scores (r=−0.615, p<0.001). ROC analysis revealed strong diagnostic efficacy with an AUC of 0.877 at the optimal cutoff value of 0.582, demonstrating 78.0 % sensitivity and 80.2 % specificity. miR-384-5p suppression attenuated Aβ-induced cytotoxicity and apoptosis (p<0.001), with SIRT1 identified as its direct target. Conclusions Altered serum levels of miR-384-5p were identified as a potential diagnostic biomarker in AD patients. Mechanistic investigations revealed that miR-384-5p downregulation exerts neuroprotective effects through targeted regulation of SIRT1, suggesting its dual significance in both disease detection and pathological mechanisms of AD.