Clinical Significance of MiR-433 in the Diagnosis of Alzheimer's Disease and Its Effect on Aβ-induced Neurotoxicity by Regulating JAK2

Background: Numerous microRNAs (miRNAs) have been investigated in the progression of Alzheimer's disease (AD). The purpose of this study was to analyze the expression of miR-433 and its diagnostic value in patients with AD, and to explore the neuroprotective effect of miR-433 in amyloid β (Aβ)-treated SH-SY5Y and SK-N-SH cells.

Methods: AD patients and AD cell model that established by Aβ treatment were used in this study. Quantitative real-time PCR was used to measure the expression of miR-433. The diagnostic value of miR-433 was evaluated using the receiver operating characteristic analysis. MTT assay was used to examine the viability of Aβ-treated SH-SY5Y and SK-N-SH cells. Bioinformatics and luciferase activity analyses were used to confirm the target gene that might be involved in the mechanisms of miR-433 in AD.

Results: Expression levels of miR-433 were decreased in AD patients and cells compared with the corresponding controls. The decreased miR-433 expression levels in serum and cerebrospinal fluid (CS) were positively correlated with MMSE scores and had relatively high diagnostic accuracy in AD patients. The gain-of-function experiments found that the overexpression of miR-433 could rescue the Aβ-induced inhibition in neuronal viability in SH-SY5Y and SK-N-SH cells. The luciferase activity results showed that JAK2 was a target gene of miR-433 in neuronal cells.

Conclusion: All the data of this study showed that miR-433 serves as a candidate diagnostic biomarker for AD patients, and may have the potential as a novel therapeutic target by ameliorating Aβ-induced neurotoxicity.