Abstract
Amyloid-β1–42 (Aβ) is thought to be a major mediator of the cognitive deficits in Alzheimer's disease. The ability of Aβ to inhibit hippocampal long-term potentiation provides a cellular correlate of this action, but the underlying molecular mechanism is only partially understood. We found that a signaling pathway involving caspase-3, Akt1 and glycogen synthase kinase-3β is an important mediator of this effect in rats and mice.
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Acknowledgements
This work was funded by the UK Alzheimer's Research Trust (K.C.), Biotechnology and Biological Sciences Research Council (K.C.), Medical Research Council (G.L.C.) and The Royal Society (J.J.). G.L.C. is a World Class University International Scholar and D.J.W. is an UK Alzheimer's Research Trust–funded Ph.D. student.
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The study was conceived by K.C. The experiments were designed by K.C., M.S. and G.L.C. and carried out by J.J., D.J.W., K.M.O., T.L.K., J.S.L., G.B., B.D. and S.S. The manuscript was written by G.L.C., M.S. and K.C.
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K.M.O., S.-C.L. and M.S. are employees of Genentech.
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Jo, J., Whitcomb, D., Olsen, K. et al. Aβ1–42 inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β. Nat Neurosci 14, 545–547 (2011). https://doi.org/10.1038/nn.2785
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DOI: https://doi.org/10.1038/nn.2785
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