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.

Optimizing preservation of extracellular vesicular miRNAs derived from clinical cerebrospinal fluid

“…While CSF EV miRNAs have been proposed as biomarkers for brain tumors [5,6] and other neurodegenerative diseases [19], it remains unclear as to the optimal conditions for storage and transport for maximizing the preservation of these samples. Undoubtedly, validation of any biomarker platform and clinical translation of such platform will require the transfer of bio-fluids between clinical centers.…”

Genomic integrity and the ageing brain

“…This family of regulatory RNAs is relevant to the current discussion because certain mi RNAs undergo ageassociated changes that affect brain function and are likely to have roles in neurodegenerative disease 152 . For example, miR-16 and miR-193B are linked to posttranscriptional control of the amyloid precursor protein (APP) expression 153,154 . In Alzheimer disease, overexpression of these two mi RNAs reduces the efficiency of APP mRNA translation both in vivo and in vitro.…”

Sphingolipid-Enriched Extracellular Vesicles and Alzheimer’s Disease: A Decade of Research

“…An additional AD exosomal miRNA biomarker was also identified [95]. miR-193b transfection of SH-SY5H cells was shown to downregulate mRNA and protein expression of APP with the 3’ untranslated region of APP mRNA containing a target for miR-193b.…”

“…miR-193b transfection of SH-SY5H cells was shown to downregulate mRNA and protein expression of APP with the 3’ untranslated region of APP mRNA containing a target for miR-193b. In APP/PS1 transgenic mice and human AD patients, miR-193b was decreased compared to wildtype mice and cognitively normal patients, respectively, in both CSF and serum exosomes [95]. However, miR-193b was not identified as a differentially expressed exosomal miRNA by the studies noted above [81–83].…”