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.
journal_name
Proc Natl Acad Sci U S Aauthors
Hébert SS,Horré K,Nicolaï L,Papadopoulou AS,Mandemakers W,Silahtaroglu AN,Kauppinen S,Delacourte A,De Strooper Bdoi
10.1073/pnas.0710263105subject
Has Abstractpub_date
2008-04-29 00:00:00pages
6415-20issue
17eissn
0027-8424issn
1091-6490pii
0710263105journal_volume
105pub_type
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