Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model
- PMID: 16136043
- DOI: 10.1038/nn1531
Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model
Abstract
In Alzheimer disease, increased beta-secretase (BACE1) activity has been associated with neurodegeneration and accumulation of amyloid precursor protein (APP) products. Thus, inactivation of BACE1 could be important in the treatment of Alzheimer disease. In this study, we found that lowering BACE1 levels using lentiviral vectors expressing siRNAs targeting BACE1 reduced amyloid production and the neurodegenerative and behavioral deficits in APP transgenic mice, a model of Alzheimer disease. Our results suggest that lentiviral vector delivery of BACE1 siRNA can specifically reduce the cleavage of APP and neurodegeneration in vivo and indicate that this approach could have potential therapeutic value for treatment of Alzheimer disease.
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