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.
Mol Med Rep
; 10(5): 2395-400, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25119742
ABSTRACT
Amyloid precursor protein (APP) has an important function in the generation of Alzheimer's disease (AD). In our previous study, miR193b was found to be downregulated in the hippocampi of 9monthold APP/PS1 doubletransgenic mice using microRNA (miR) array. In the present study, bioinformatic analyses showed that miR193b was a miR that was predicted to potentially target the 3'untranslated region (UTR) of APP. Subsequently, the function of miR193b on APP was studied. The levels of miR193b, exosomal miR193b, Aß, tau, ptau, HCY and APOE in samples from APP/PS1 doubletransgenic mice, mild cognitive impairment (MCI) and dementia of Alzheimertype (DAT) patients, were measured. The results indicated that overexpression of miR193b could repress the mRNA and protein expression of APP. The miR193b inhibitor oligonucleotide induced upregulation of APP. Binding sites of miR193b in the 3'UTR of APP were identified by luciferase assay. MCI and DAT patients had lower exosomal miR193b, but not total miR193b, in the blood as compared with the controls. DAT patients had lower exosomal miR193b levels in blood as compared with the MCI group. A decreased exosomal miR193b expression level was additionally observed in the cerebral spinal fluid (CSF) of DAT patients. Negative correlations were found between exosomal miR193b and Aß42 in the CSF of DAT patients. In conclusion, these findings showed that miR193b may function in the development of AD and exosomal miR193b has potential as a novel, non-invasive, bloodbased biomarker of MCI and DAT patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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MicroRNAs
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Doença de Alzheimer
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article