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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\u03b2 peptide. Second, testing for neurodegeneration and amyloid deposits, we investigated retromer-deficient flies expressing human wild-type amyloid precursor protein (APP) and human \u03b2-site APP-cleaving enzyme (BACE) and found that they develop neuronal loss and human A\u03b2 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.<\/jats:p>","DOI":"10.1073\/pnas.0802545105","type":"journal-article","created":{"date-parts":[[2008,5,14]],"date-time":"2008-05-14T21:10:01Z","timestamp":1210799401000},"page":"7327-7332","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":242,"title":["Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and A\u03b2 accumulation"],"prefix":"10.1073","volume":"105","author":[{"given":"Alim","family":"Muhammad","sequence":"first","affiliation":[{"name":"*Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Flores","sequence":"additional","affiliation":[{"name":"*Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"*Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and"},{"name":"Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032; 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