期刊
JOURNAL OF NEUROSCIENCE
卷 29, 期 31, 页码 9704-9713出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2292-09.2009
关键词
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资金
- Alzheimer's Association New Investigator Award
- Zenith Award
- Appel Foundation
- National Institute of Health [AG20729, AG027140, AG028174, AG09464]
- University of Minnesota
A central question in Alzheimer's disease research is what role synaptic activity plays in the disease process. Synaptic activity has been shown to induce beta-amyloid peptide release into the extracellular space, and extracellular beta-amyloid has been shown to be toxic to synapses. We now provide evidence that the well established synaptotoxicity of extracellular beta-amyloid requires gamma-secretase processing of amyloid precursor protein. Recent evidence supports an important role for intraneuronal beta-amyloid in the pathogenesis of Alzheimer's disease. We show that synaptic activity reduces intraneuronal beta-amyloid and protects against beta-amyloid-related synaptic alterations. We demonstrate that synaptic activity promotes the transport of the amyloid precursor protein to synapses using live cell imaging, and that the protease neprilysin is involved in reduction of intraneuronal beta-amyloid with synaptic activity.
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