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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2017

Open Access 01-12-2017 | Research article

Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease

Authors: Ellis Patrick, Sathyapriya Rajagopal, Hon-Kit Andus Wong, Cristin McCabe, Jishu Xu, Anna Tang, Selina H. Imboywa, Julie A. Schneider, Nathalie Pochet, Anna M. Krichevsky, Lori B. Chibnik, David A. Bennett, Philip L. De Jager

Published in: Molecular Neurodegeneration | Issue 1/2017

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Abstract

Background

Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer’s disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer’s disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region.

Methods

We report analyses of expression profiling of miRNA (n = 700 subjects) and lincRNA (n = 540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging.

Results

We confirm the association of two well-established miRNA (miR-132, miR-129) with pathologic AD in our dataset and then further characterize this association in terms of its component neuritic β-amyloid plaques and neurofibrillary tangle pathologies. Additionally, we identify one new miRNA (miR-99) and four lincRNA that are associated with these traits. Many other previously reported associations of microRNA with AD are associated with the confounders quantified in our longitudinal cohort. Finally, by performing analyses integrating both miRNA and RNA sequence data from the same individuals (525 samples), we characterize the impact of AD associated miRNA on human brain expression: we show that the effects of miR-132 and miR-129-5b converge on certain genes such as EP300 and find a role for miR200 and its target genes in AD using an integrated miRNA/mRNA analysis.

Conclusions

Overall, miRNAs play a modest role in human AD, but we observe robust evidence that a small number of miRNAs are responsible for specific alterations in the cortical transcriptome that are associated with AD.
Appendix
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Metadata
Title
Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease
Authors
Ellis Patrick
Sathyapriya Rajagopal
Hon-Kit Andus Wong
Cristin McCabe
Jishu Xu
Anna Tang
Selina H. Imboywa
Julie A. Schneider
Nathalie Pochet
Anna M. Krichevsky
Lori B. Chibnik
David A. Bennett
Philip L. De Jager
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-017-0191-y

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