Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression.

TLDR: It is shown here that miR-29a, -29b-1, and -9 can regulate Bace1 expression in vitro and proposed that loss of specific miRNAs can contribute to increased BACE1 and Aβ levels in sporadic AD.

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 A generation in sporadic AD. Deficiency in A clearance is certainly a possibility, but increased expression of proteins like APP or BACE1/-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 signifi- cantly (and AD-dementia-specific) decreased in AD patients dis- playing abnormally high BACE1 protein. Similar correlations be- tween 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 A generation in a cell culture model. We propose that loss of specific miRNAs can contribute to in- creased BACE1 and A levels in sporadic AD. neurodegeneration amyloid noncoding RNA