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We now show that levels of secreted A\u03b2 fall with time in culture in neurons of AD-transgenic mice, but not wild-type mice. Moreover, the ability of synaptic activity to elevate secreted A\u03b2 and reduce intraneuronal A\u03b2 becomes impaired in AD-transgenic but not wild-type neurons with time in culture. We demonstrate that synaptic activity promotes an increase in the A\u03b2-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with A\u03b242. Remarkably, AD-transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete A\u03b2 and reduce intraneuronal A\u03b2 has important implications for the pathogenesis and treatment of AD.<\/jats:p>","DOI":"10.1523\/jneurosci.2986-11.2011","type":"journal-article","created":{"date-parts":[[2011,10,26]],"date-time":"2011-10-26T17:05:00Z","timestamp":1319648700000},"page":"15384-15390","source":"Crossref","is-referenced-by-count":38,"title":["Impaired \u03b2-Amyloid Secretion in Alzheimer's Disease Pathogenesis"],"prefix":"10.1523","volume":"31","author":[{"given":"Davide","family":"Tampellini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawreen","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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