Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory
Article first published online: 6 APR 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 69, Issue 5, pages 819–830, May 2011
How to Cite
Puzzo, D., Privitera, L., Fa', M., Staniszewski, A., Hashimoto, G., Aziz, F., Sakurai, M., Ribe, E. M., Troy, C. M., Mercken, M., Jung, S. S., Palmeri, A. and Arancio, O. (2011), Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory. Ann Neurol., 69: 819–830. doi: 10.1002/ana.22313
- Issue published online: 22 APR 2011
- Article first published online: 6 APR 2011
- Accepted manuscript online: 28 OCT 2010 07:27AM EST
- Manuscript Accepted: 15 OCT 2010
- Manuscript Revised: 10 SEP 2010
- Manuscript Received: 12 JAN 2010
The goal of this study was to investigate the role of endogenous amyloid-β peptide (Aβ) in healthy brain.
Long-term potentiation (LTP), a type of synaptic plasticity that is thought to be associated with learning and memory, was examined through extracellular field recordings from the CA1 region of hippocampal slices, whereas behavioral techniques were used to assess contextual fear memory and reference memory. Amyloid precursor protein (APP) expression was reduced through small interfering RNA (siRNA) technique.
We found that both antirodent Aβ antibody and siRNA against murine APP reduced LTP as well as contextual fear memory and reference memory. These effects were rescued by the addition of human Aβ42, suggesting that endogenously produced Aβ is needed for normal LTP and memory. Furthermore, the effect of endogenous Aβ on plasticity and memory was likely due to regulation of transmitter release, activation of α7-containing nicotinic acetylcholine receptors, and Aβ42 production.
Endogenous Aβ42 is a critical player in synaptic plasticity and memory within the normal central nervous system. This needs to be taken into consideration when designing therapies aiming at reducing Aβ levels to treat Alzheimer disease. Ann Neurol 2011;