Title: Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression
Authors: Hébert, Sébastien
Horré, Katrien
Nicolaï, Laura
Papadopoulou, Aikaterini
Mandemakers, Wilhelm
Silahtaroglu, Asli N
Kauppinen, Sakari
Delacourte, André
De Strooper, Bart # ×
Issue Date: 29-Apr-2008
Publisher: National Academy of Sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:105 issue:17 pages:6415-20
Abstract: Although the role of APP and PSEN genes in genetic Alzheimer's disease (AD) cases is well established, fairly little is known about the molecular mechanisms affecting Abeta generation in sporadic AD. Deficiency in Abeta clearance is certainly a possibility, but increased expression of proteins like APP or BACE1/beta-secretase may also be associated with the disease. We therefore investigated changes in microRNA (miRNA) expression profiles of sporadic AD patients and found that several miRNAs potentially involved in the regulation of APP and BACE1 expression appeared to be decreased in diseased brain. We show here that miR-29a, -29b-1, and -9 can regulate BACE1 expression in vitro. The miR-29a/b-1 cluster was significantly (and AD-dementia-specific) decreased in AD patients displaying abnormally high BACE1 protein. Similar correlations between expression of this cluster and BACE1 were found during brain development and in primary neuronal cultures. Finally, we provide evidence for a potential causal relationship between miR-29a/b-1 expression and Abeta generation in a cell culture model. We propose that loss of specific miRNAs can contribute to increased BACE1 and Abeta levels in sporadic AD.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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