Neuronal microrna deregulation in response to Alzheimer's disease amyloid-β

Schonrock, Nicole, Ke, Yazi D., Humphreys, David, Staufenbiel, Matthias, Ittner, Lars M., Preiss, Thomas and Gotz, Jurgen (2010) Neuronal microrna deregulation in response to Alzheimer's disease amyloid-β. PLoS ONE, 5 6: e11070.1-e11070.11. doi:10.1371/journal.pone.0011070

Author Schonrock, Nicole
Ke, Yazi D.
Humphreys, David
Staufenbiel, Matthias
Ittner, Lars M.
Preiss, Thomas
Gotz, Jurgen
Title Neuronal microrna deregulation in response to Alzheimer's disease amyloid-β
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2010-06
Year available 2010
Sub-type Article (original research)
DOI 10.1371/journal.pone.0011070
Open Access Status DOI
Volume 5
Issue 6
Start page e11070.1
End page e11070.11
Total pages 11
Place of publication San Francisco United States
Publisher Public Library of Science (PLoS)
Language eng
Formatted abstract
Normal brain development and function depends on microRNA (miRNA) networks to fine tune the balance between the transcriptome and proteome of the cell. These small non-coding RNA regulators are highly enriched in brain where they play key roles in neuronal development, plasticity and disease. In neurodegenerative disorders such as Alzheimer's disease (AD), brain miRNA profiles are altered; thus miRNA dysfunction could be both a cause and a consequence of disease. Our study dissects the complexity of human AD pathology, and addresses the hypothesis that amyloid-β (Aβ) itself, a known causative factor of AD, causes neuronal miRNA deregulation, which could contribute to the pathomechanisms of AD. We used sensitive TaqMan low density miRNA arrays (TLDA) on murine primary hippocampal cultures to show that about half of all miRNAs tested were down-regulated in response to Aβ peptides. Time-course assays of neuronal Aβ treatments show that Aβ is in fact a powerful regulator of miRNA levels as the response of certain mature miRNAs is extremely rapid. Bioinformatic analysis predicts that the deregulated miRNAs are likely to affect target genes present in prominent neuronal pathways known to be disrupted in AD. Remarkably, we also found that the miRNA deregulation in hippocampal cultures was paralleled in vivo by a deregulation in the hippocampus of Aβ42-depositing APP23 mice, at the onset of Aβ plaque formation. In addition, the miRNA deregulation in hippocampal cultures and APP23 hippocampus overlaps with those obtained in human AD studies. Taken together, our findings suggest that neuronal miRNA deregulation in response to an insult by Aβ may be an important factor contributing to the cascade of events leading to AD.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 81 times in Thomson Reuters Web of Science Article | Citations
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