Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., Malinow, R. (March 2003) APP processing and synaptic function. Neuron, 37 (6). pp. 925-937. ISSN 0896-6273
Abstract
A large body of evidence has implicated Abeta peptides and other derivatives of the amyloid precursor protein (APP) as central to the pathogenesis of Alzheimer's disease (AD). However, the functional relationship of APP and its proteolytic derivatives to neuronal electrophysiology is not known. Here, we show that neuronal activity modulates the formation and secretion of Abeta peptides in hippocampal slice neurons that overexpress APP. In turn, Abeta selectively depresses excitatory synaptic transmission onto neurons that overexpress APP, as well as nearby neurons that do not. This depression depends on NMDA-R activity and can be reversed by blockade of neuronal activity. Synaptic depression from excessive Abeta could contribute to cognitive decline during early AD. In addition, we propose that activity-dependent modulation of endogenous Abeta production may normally participate in a negative feedback that could keep neuronal hyperactivity in check. Disruption of this feedback system could contribute to disease progression in AD.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | AMYLOID-PRECURSOR PROTEIN LONG-TERM POTENTIATION FAMILIAL ALZHEIMERS-DISEASE HIPPOCAMPUS IN-VIVO BETA-PROTEIN TRANSGENIC MICE AMPA RECEPTORS A-BETA MEMORY DEFICITS NERVOUS-SYSTEM |
| Subjects: | diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease diseases & disorders > mental disorders > delirium dementia cognitive disorders diseases & disorders organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse |
| CSHL Authors: | |
| Communities: | CSHL labs > Malinow lab |
| Depositing User: | Matt Covey |
| Date: | March 2003 |
| Date Deposited: | 28 Jun 2013 18:37 |
| Last Modified: | 28 Jun 2013 18:37 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27909 |
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