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Molecular Neurodegeneration

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Open Access 01-12-2011 | Short report

Alzheimer-specific variants in the 3'UTR of Amyloid precursor protein affect microRNA function

Authors: Charlotte Delay, Frédéric Calon, Paul Mathews, Sébastien S Hébert

Published in: Molecular Neurodegeneration | Issue 1/2011

Abstract

Background

APP expression misregulation can cause genetic Alzheimer's disease (AD). Recent evidences support the hypothesis that polymorphisms located in microRNA (miRNA) target sites could influence the risk of developing neurodegenerative disorders such as Parkinson's disease (PD) and frontotemporal dementia. Recently, a number of single nucleotide polymorphisms (SNPs) located in the 3'UTR of APP have been found in AD patients with family history of dementia. Because miRNAs have previously been implicated in APP expression regulation, we set out to determine whether these polymorphisms could affect miRNA function and therefore APP levels.

Results

Bioinformatics analysis identified twelve putative miRNA bindings sites located in or near the APP 3'UTR variants T117C, A454G and A833C. Among those candidates, seven miRNAs, including miR-20a, miR-17, miR-147, miR-655, miR-323-3p, miR-644, and miR-153 could regulate APP expression in vitro and under physiological conditions in cells. Using luciferase-based assays, we could show that the T117C variant inhibited miR-147 binding, whereas the A454G variant increased miR-20a binding, consequently having opposite effects on APP expression.

Conclusions

Taken together, our results provide proof-of-principle that APP 3'UTR polymorphisms could affect AD risk through modulation of APP expression regulation, and set the stage for further association studies in genetic and sporadic AD.

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Title: Alzheimer-specific variants in the 3'UTR of Amyloid precursor protein affect microRNA function
Authors: Charlotte Delay
Frédéric Calon
Paul Mathews
Sébastien S Hébert
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2011
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-6-70

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Alzheimer-specific variants in the 3'UTR of Amyloid precursor protein affect microRNA function

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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