Deficits in synaptic transmission and learning in amyloid precursor protein (APP) transgenic mice require C-terminal cleavage of APP

被引:108
作者
Saganich, Michael J.
Schroeder, Brock E.
Galvan, Veronica
Bredesen, Dale E.
Koo, Edward H.
Heinemann, Stephen F.
机构
[1] Salk Inst Biol Studies, La Jolla, CA 92037 USA
[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA
[3] Buck Inst Age Res, Novato, CA 94945 USA
关键词
A beta-peptide; potentiation; Schaffer collateral terminals; synaptic plasticity; hippocampus; learning memory; spatial memory; LTP; amyloid; Alzheimer's disease;
D O I
10.1523/JNEUROSCI.4180-06.2006
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Synaptic dysfunction has been shown to be one of the earliest correlates of disease progression in animal models of Alzheimer's disease. Amyloid-beta protein (A beta) is thought to play an important role in disease-related synaptic dysfunction, but the mechanism by which A beta leads to synaptic dysfunction is not understood. Here we describe evidence that cleavage of APP in the C terminus may be necessary for the deficits present in APP transgenic mice. In APP transgenic mice with a mutated cleavage site at amino acid 664, normal synaptic transmission, synaptic plasticity, and learning were maintained despite the presence of elevated levels of APP, A beta(42), and even plaque accumulation. These results indicate that cleavage of APP may play a critical role in the development of synaptic and behavioral dysfunction in APP transgenic mice.
引用
收藏
页码:13428 / 13436
页数:9
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