Background <p>Neuroinflammation mediated by microglial polarization is a critical pathological process in Alzheimer’s disease (AD). Long non-coding RNAs (lncRNAs) have emerged as key regulators in this process, but the role of LINC00926 remains unexplored.</p> Methods <p>Serum was obtained from 91 AD patients and 78 healthy controls (HCs), and qRT-PCR was used to quantify LINC00926 and miR-383-3p expression. Their diagnostic value and correlation with clinical indicators were analyzed via ROC curve and correlation analyses. A dual-luciferase assay verified their direct binding. In vitro studies, an AD cell model was created by treating BV2 microglial cells with Aβ₁₋₄₂. The role of the LINC00926/miR-383-3p axis in microglial polarization and inflammatory cytokine secretion was evaluated using qPCR and ELISA.</p> Results <p>Serum LINC00926 was significantly downregulated in AD patients, while miR-383-3p was upregulated compared to HCs. ROC analysis showed that LINC00926 and miR-383-3p possessed high diagnostic value for AD, with AUCs of 0.825 and 0.787, respectively. Their expression levels were significantly correlated with MMSE scores and CSF biomarkers (Aβ₁₋₄₂, t-tau, p-tau). Dual-luciferase assay verified that LINC00926 directly binds to miR-383-3p. In Aβ₁₋₄₂-induced BV2 cells, overexpression of LINC00926 suppressed M1 polarization (decreased iNOS, TNF-α, IL-1β) and promoted M2 polarization (decreased Arg1, TGF-β, IL-10), whereas these effects were reversed by co-transfection with a miR-383-3p mimic.</p> Conclusion <p>LINC00926 sponges miR-383-3p to promote microglial M1 polarization and neuroinflammation in AD, highlighting the LINC00926/miR-383-3p axis as a potential diagnostic biomarker and therapeutic target.</p>