MiR-485-3p Serves As a Biomarker and Therapeutic Target of Alzheimer's Disease Via Regulating Neuronal Cell Viability and Neuroinflammation by Targeting AKT3

Background: Numerous microRNAs (miRNAs) have been identified as functional molecules in Alzheimer's disease (AD) pathogenesis. This study aimed to investigate the diagnostic value of microRNA-485-3p (miR-485-3p) in AD patients, evaluate the effect of miR-485-3p on neuronal viability and neuroinflammation, as well as the underlying molecular mechanisms.

Methods: Quantitative Real-Time PCR was used to estimate expression of miR-485-3p and AKT3. A ROC analysis was used to evaluate the diagnostic value of miR-485-3p. The correlation of miR-485-3p with patients' MMSE score and inflammatory response was analyzed. Using Aβ-treated SH-SY5Y and BV2 cells models, the effects of miR-485-3p on neuronal proliferation, apoptosis, and neuroinflammation were explored. A luciferase reporter assay was used to confirm the target gene of miR-485-3p in both SH-SY5Y and BV2 cells.

Results: Serum miR-485-3p expression was significantly upregulated in AD patients and cell models, which had a high diagnostic accuracy and correlated with MMSE score and inflammatory response in AD patients. The knockdown of miR-485-3p in SH-SY5Y and BV2 cells was found to significantly reverse the effect of Aβ treatment on neuronal viability and neuroinflammation. AKT3 was determined as a target of miR-485-3p, which might mediate the biological function of miR-485-3p in AD pathogenesis.

Conclusion: All the data indicated that increased serum miR-485-3p serves as a diagnostic biomarker in AD patients, and knockdown of miR-485-3p exerts a neuroprotective role by improving neuronal viability and weakening neuroinflammation, which may be mediated by AKT3. This study may provide a novel biomarker and therapeutic target for AD therapy.