Get started
Work

Deficits in Synaptic Transmission and Learning in Amyloid Precursor Protein (APP) Transgenic Mice Require C-Terminal Cleavage of APP

Year: 2006
Type: article
Abstract: 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 (Abeta) is thought to play an important role in disease-related synaptic dysfunction, but the mechanism by which Abeta 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, Abeta42, 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.
DOI: 10.1523/jneurosci.4180-06.2006
Authors: Michael J. Saganich, Brock E. Schroeder, Veronica Galvan, Dale E. Bredesen, Edward H. Koo, Stephen F. Heinemann
Language: English
Open Access status: hybrid
Funders: Ellison Medical Foundation, Alzheimer's Association, Fidelity Foundation, National Institutes of Health, Directorate for Biological Sciences, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development
Awards: G1019915673, Gene Therapy for Alzheimer's Disease, UCSD Alzheimer's Disease Research Center P50, G4055135756, G4727279016, Training in the Neuroplasticity of Aging, Mechanism of apoptosis induction by the receptor DCC, G9000191018
OpenAlex ID: W2019061059
FWCI: 3.141
Cites: 41
Cited by: 135
Related to: 10