RT Journal Article
SR Electronic
T1 Synaptic Activity Reduces Intraneuronal Aβ, Promotes APP Transport to Synapses, and Protects against Aβ-Related Synaptic Alterations
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9704
OP 9713
DO 10.1523/JNEUROSCI.2292-09.2009
VO 29
IS 31
A1 Davide Tampellini
A1 Nawreen Rahman
A1 Eduardo F. Gallo
A1 Zhenyong Huang
A1 Magali Dumont
A1 Estibaliz Capetillo-Zarate
A1 Tao Ma
A1 Rong Zheng
A1 Bao Lu
A1 David M. Nanus
A1 Michael T. Lin
A1 Gunnar K. Gouras
YR 2009
UL http://www.jneurosci.org/content/29/31/9704.abstract
AB 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 β-amyloid peptide release into the extracellular space, and extracellular β-amyloid has been shown to be toxic to synapses. We now provide evidence that the well established synaptotoxicity of extracellular β-amyloid requires γ-secretase processing of amyloid precursor protein. Recent evidence supports an important role for intraneuronal β-amyloid in the pathogenesis of Alzheimer's disease. We show that synaptic activity reduces intraneuronal β-amyloid and protects against β-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 β-amyloid with synaptic activity.