The clinical significance of miR-484 in depression of older people with Alzheimer’s disease and its potential role on depressive behavior

Objective MicroRNAs exhibit remarkable potential as biomarkers due to their multiple advantages in Alzheimer’s disease (AD). This study aimed to explore the significance of miR-484 in AD. Methods The study included 216 participants 70 healthy controls (HCs), 77 AD with nondepression, 69 AD with depression (AD-D). PCR measured serum and tissue miR-484 levels. Receiver operator characteristic curves evaluated miR-484 diagnostic potential for AD/AD-D. Logistic regression identified AD-D risk factors. Bioinformatics predicted miR-484 targets and functional pathways. Dual-luciferase assay validated the interaction between miR-484 and platelet derived growth factor subunit A (PDGFA). Chronic restraint stress (CRS) induced depression animal model by Kunming mice (20 each group × 6 groups). The effect of miR-484/PDGFA axis on depression-like behaviors was evaluated through behavioral tests (sucrose preference, forced swim, and open field). Results Serum miR-484 was downregulated in AD and further decreased in AD-D compared with HCs. MiR-484 downregulation diagnosed AD-D from AD. MiR-484 expression was correlated with amyloid β -protein 1–42 ( r = 0.682), total tau ( r = −0.575), Mini-Mental State Examination score ( r = 0.593), and Hamilton depression rating scale score ( r = −0.709). MiR-484 was a risk factor for depression in AD. In the depression mouse model, miR-484 overexpression ameliorated depression-like behaviors (sucrose preference, forced swim immobility time, locomotor activity) by regulating PDGFA. Conclusion Downregulated miR-484 expression, correlating with cognitive function and depression degree, showed a diagnostic value on AD and AD-D. MiR-484 attenuated the CRS-induced depression-like behavior by regulating PDGFA.