Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation

@article{citeulike:2801973, abstract = {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}, author = {Muhammad, Alim and Flores, Ingrid and Zhang, Hong and Yu, Rui and Staniszewski, Agnieszka and Planel, Emmanuel and Herman, Mathieu and Ho, Lingling and Kreber, Robert and Honig, Lawrence S. and Ganetzky, Barry and Duff, Karen and Arancio, Ottavio and Small, Scott A. }, citeulike-article-id = {2801973}, doi = {10.1073/pnas.0802545105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {retromer}, month = {May}, pages = {0802545105+}, posted-at = {2008-05-15 16:14:12}, priority = {2}, title = {Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and A{beta} accumulation}, url = {http://dx.doi.org/10.1073/pnas.0802545105}, year = {2008} }

TY - JOUR ID - citeulike:2801973 L3 - citeulike-article-id:2801973 TI - Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and A{beta} accumulation JF - Proceedings of the National Academy of Sciences SP - 0802545105 N2 - 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 KW - retromer AU - Muhammad, Alim AU - Flores, Ingrid AU - Zhang, Hong AU - Yu, Rui AU - Staniszewski, Agnieszka AU - Planel, Emmanuel AU - Herman, Mathieu AU - Ho, Lingling AU - Kreber, Robert AU - Honig, Lawrence AU - Ganetzky, Barry AU - Duff, Karen AU - Arancio, Ottavio AU - Small, Scott PY - 2008/05/14/ UR - http://dx.doi.org/10.1073/pnas.0802545105 ER -