{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:27:49Z","timestamp":1791289669600,"version":"4.3.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,4,15]]},"abstract":"<jats:p>\n                    \u03b2-amyloid protein (A\u03b2) formation was reconstituted in permeabilized neuroblastoma cells expressing human Alzheimer \u03b2-amyloid precursor protein (\u03b2APP) harboring the Swedish double mutation associated with familial early-onset Alzheimer disease. Permeabilized cells were prepared following metabolic labeling and incubation at 20\u00b0C, a temperature that allows \u03b2APP to accumulate in the trans-Golgi network (TGN) without concomitant A\u03b2 formation. Subsequent incubation at 37\u00b0C led to the generation of A\u03b2. A\u03b2 production in the TGN persisted even under conditions in which formation of nascent post-TGN vesicles was inhibited by addition of guanosine 5\u2032-\n                    <jats:italic>O<\/jats:italic>\n                    -(3-thiotriphosphate), a nonhydrolyzable GTP analogue, or by omission of cytosol. These and other results indicate that vesicle budding and trafficking may not be required for proteolytic metabolism of \u03b2APP to A\u03b2, a process that includes \u201c\u03b3-secretase\u201d cleavage within the \u03b2APP transmembrane domain.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.8.3748","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"3748-3752","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":231,"title":["Generation of Alzheimer \u03b2-amyloid protein in the trans-Golgi network in the apparent absence of vesicle\u2009formation"],"prefix":"10.1073","volume":"94","author":[{"given":"Huaxi","family":"Xu","sequence":"first","affiliation":[{"name":"Laboratory of Alzheimer Research, Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021; Laboratory of Molecular and Cellular Neuroscience and Fisher Center for Research on Alzheimer Disease, and Laboratory for Mass Spectrometry, The Rockefeller University, New York, NY 10021; and Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Laboratory of Alzheimer Research, Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021; Laboratory of Molecular and Cellular Neuroscience and Fisher Center for Research on Alzheimer Disease, and Laboratory for Mass Spectrometry, The Rockefeller University, New York, NY 10021; and Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Alzheimer Research, Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021; Laboratory of Molecular and Cellular Neuroscience and Fisher Center for Research on Alzheimer Disease, and Laboratory for Mass Spectrometry, The Rockefeller University, New York, NY 10021; and Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopal","family":"Thinakaran","sequence":"additional","affiliation":[{"name":"Laboratory of Alzheimer Research, Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021; Laboratory of Molecular and Cellular Neuroscience and Fisher Center for Research on Alzheimer Disease, and Laboratory for Mass Spectrometry, The Rockefeller University, New York, NY 10021; and Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C. 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