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Neurodegenerative disease

Meet the mediator, but not as you know it

Nature Reviews Neuroscience volume 12, pages 66–67 (2011)Cite this article

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The authors used Tg2576 transgenic mice, which carry a human form of amyloid precursor protein (APP) associated with Alzheimer's disease. At 3 months of age, Tg2576 mice were impaired in a hippocampus-dependent cognitive test compared with wild-type mice, and showed structural spine alterations and altered glutamate transmission in the hippocampus. Moreover, hippocampal postsynaptic density (PSD) extracts of Tg2576 mice had reduced levels of both the GluR1 subunit of the AMPA receptor and its phosphorylated form GluR1pSer845.

As caspase-3 activity in Alzheimer's disease has been associated with neuronal loss, the authors next examined whether altered caspase-3 activity also underlies the synaptic alterations in Tg2576 mice. Caspase-3 activity was increased in the synaptosomal fraction of hippocampal extracts of 3-month-old (but not 2-month-old) Tg2576 mice compared with wild-type mice, and the PSD of hippocampal spines in Tg2576 mice showed immunostaining for activated caspase-3. Surprisingly, the authors found no evidence of hippocampal apoptosis in Tg2576 or wild-type mice.

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ORIGINAL RESEARCH PAPER

  1. D'Amelio, M. et al. Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease. Nature Neurosci. 14, 69–76 (2011)

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  1. Leonie Welberg
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Welberg, L. Meet the mediator, but not as you know it. Nat Rev Neurosci 12, 66–67 (2011). https://doi.org/10.1038/nrn2983

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