title: 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.
abstract: 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, Aβ, 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 Aβ42 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.
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Chen-Geng
authors.initials: CG
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Yue-Qi
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Pei-Chang
authors.initials: PC
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D055354:Exosomes / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000134:cerebrospinal fluid / Q000235:genetics*; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000235:genetics; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; D015415:Biomarkers; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)