{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:34:24Z","timestamp":1777419264632,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2002,3,6]],"date-time":"2002-03-06T00:00:00Z","timestamp":1015372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2002,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Limiting beta amyloid (A\u03b2) production could become an important therapeutic target in Alzheimer's disease (AD). A\u03b2 is derived by the sequential cleavage of amyloid precursor protein (APP) by \u03b2\u2010 and \u03b3\u2010secretases. A double missense mutation in APP found in a Swedish pedigree (APPsw) elevates A\u03b240 and A\u03b242 production. A\u03b2 production and, therefore, \u03b2\u2010secretase cleavage of APPsw reportedly occur in the endoplasmic reticulum (ER), Golgi and endocytic compartments. However, the relative contribution of \u03b2\u2010secretase cleavage occurring in each compartment has not been determined. Experiments described here use a novel ELISA to measure the \u03b2\u2010cleaved product, APPsw\u03b2. Using this ELISA, we provide new information regarding the relative amount of \u03b2\u2010secretase cleavage of APPsw that occurs in secretory and endocytic pathways. Using a dilysine retrieval motif to retain APPsw in the ER, we discovered that less than 15% of the \u03b2\u2010secretase cleavage was still detected. Experiments utilizing endocytosis\u2010impaired mutants of APPsw revealed that little or no \u03b2\u2010secretase cleavage of APPsw appears to take place through endocytosis. Surprisingly, deletion of the entire cytoplasmic tail increased both APPsw\u03b2 and A\u03b2 secretion, suggesting that protein interactions with this region normally impede \u03b2\u2010secretase cleavage. These results suggest that APPsw is cleaved by \u03b2\u2010secretase late in the secretory pathway.<\/jats:p>","DOI":"10.1046\/j.0022-3042.2002.00764.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T06:59:55Z","timestamp":1047452395000},"page":"1019-1028","source":"Crossref","is-referenced-by-count":25,"title":["ELISA analysis of \u03b2\u2010secretase cleavage of the Swedish amyloid precursor protein in the secretory and endocytic pathways"],"prefix":"10.1111","volume":"80","author":[{"given":"Michelle L.","family":"Steinhilb","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Scott","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Gaut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,3,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.147.2.277"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.11.6229"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.19.11339"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.3.671"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90323-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.25.11993"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0997-1021"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.1.61"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.51.32247"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.20.10832"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295-1291"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002095200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0997-1016"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-17-07507.1999"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0811"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.121.2.317"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"17386","DOI":"10.1016\/S0021-9258(17)32449-3","article-title":"Evidence that production and release of amyloid beta\u2010protein involves the endocytic pathway","volume":"269","author":"Koo E. 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