Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein

作者：Gimbel David A; Nygaard Haakon B; Coffey Erin E; Gunther Erik C; Lauren Juha; Gimbel Zachary A; Strittmatter Stephen M^*

来源：Journal of Neuroscience, 2010, 30(18): 6367-6374.

DOI：10.1523/JNEUROSCI.0395-10.2010

Soluble oligomers of the amyloid-beta (A beta) peptide are thought to play a key role in the pathophysiology of Alzheimer's disease (AD). Recently, we reported that synthetic A beta oligomers bind to cellular prion protein (PrP(C)) and that this interaction is required for suppression of synaptic plasticity in hippocampal slices by oligomeric A beta peptide. We hypothesized that PrP(C) is essential for the ability of brain-derived A beta to suppress cognitive function. Here, we crossed familial AD transgenes encoding APPswe and PSen1 Delta E9 into Prnp(-/-) mice to examine the necessity of PrP(C) for AD-related phenotypes. Neither APP expression nor A beta level is altered by PrP(C) absence in this transgenic AD model, and astrogliosis is unchanged. However, deletion of PrP(C) expression rescues 5-HT axonal degeneration, loss of synaptic markers, and early death in APPswe/ PSen1 Delta E9 transgenic mice. The AD transgenic mice with intact PrP(C) expression exhibit deficits in spatial learning and memory.

• 出版日期2010-5-5