Thu, 21 Aug 2008 01:17:47 BST CiteULike: giovanni's Ganetzky http://www.citeulike.org/user/giovanni/author/Ganetzky CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/giovanni/article/2801973 <i>Proceedings of the National Academy of Sciences (14 May 2008), 0802545105.</i><br /><br />Although deficiencies in the retromer sorting pathway have been linked to late-onset Alzheimer's disease, whether these deficiencies underlie the disease remains unknown. Here we characterized two genetically modified animal models to test separate but related questions about the effects that retromer deficiency has on the brain. First, testing for cognitive defects, we investigated retromer-deficient mice and found that they develop hippocampal-dependent memory and synaptic dysfunction, which was associated with elevations in endogenous A peptide. Second, testing for neurodegeneration and amyloid deposits, we investigated retromer-deficient flies expressing human wild-type amyloid precursor protein (APP) and human -site APP-cleaving enzyme (BACE) and found that they develop neuronal loss and human A aggregates. By recapitulating features of the disease, these animal models suggest that retromer deficiency observed in late-onset Alzheimer's disease can contribute to disease pathogenesis. 10.1073/pnas.0802545105 Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation Alim Muhammad Ingrid Flores Hong Zhang Rui Yu Agnieszka Staniszewski Emmanuel Planel Mathieu Herman Lingling Ho Robert Kreber Lawrence Honig Barry Ganetzky Karen Duff Ottavio Arancio Scott Small doi:10.1073/pnas.0802545105 Proceedings of the National Academy of Sciences (14 May 2008), 0802545105. 2008-05-15T15:14:02-00:00 2008 Proceedings of the National Academy of Sciences 0802545105 retromer