MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease

Amyloid precursor protein (APP) has an important function in the generation of Alzheimer's disease (AD). In our previous study, miR-193b was found to be downregulated in the hippocampi of 9-month-old APP/PS1 double-transgenic mice using microRNA (miR) array. In the present study, bioinformatic analyses showed that miR-193b was a miR that was predicted to potentially target the 3'-untranslated region (UTR) of APP. Subsequently, the function of miR-193b on APP was studied. The levels of miR-193b, exosomal miR-193b, A beta, tau, p-tau, HCY and APOE in samples from APP/PS1 double-transgenic mice, mild cognitive impairment (MCI) and dementia of Alzheimer-type (DAT) patients, were measured. The results indicated that overexpression of miR-193b could repress the mRNA and protein expression of APP. The miR-193b inhibitor oligonucleotide induced upregulation of APP. Binding sites of miR-193b in the 3'-UTR of APP were identified by luciferase assay. MCI and DAT patients had lower exosomal miR-193b, but not total miR-193b, in the blood as compared with the controls. DAT patients had lower exosomal miR-193b levels in blood as compared with the MCI group. A decreased exosomal miR-193b expression level was additionally observed in the cerebral spinal fluid (CSF) of DAT patients. Negative correlations were found between exosomal miR-193b and A beta 42 in the CSF of DAT patients. In conclusion, these findings showed that miR-193b may function in the development of AD and exosomal miR-193b has potential as a novel, non-invasive, blood-based biomarker of MCI and DAT patients.