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This effect implies that changes of protein expression in neuronal cells with calcium stress should provide a molecular marker for this disease. In the present study, we used the supernatant from a neuronal cell culture after incubation with or without A\u03b2 and isolated a Ca<jats:sup>2+<\/jats:sup>\u2010dependent acidic phospholipid binding fraction to perform a proteomic study. Several unique proteins were identified after incubation with A\u03b2. We focused on annexin A5, among these proteins, because it binds both Ca<jats:sup>2+<\/jats:sup> and lipids likely to be involved in calcium homeostasis. Tg2576 transgenic mice (AD model) overexpressing mutant human APP showed a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. In human plasma samples, the level of annexin A5 was significantly increased in a proportion of AD patients compared with a control group (<jats:italic>P<\/jats:italic> &lt; 0.0001 in the logistic regression analysis). From the receiver operating characteristic (ROC) curve with plasma annexin A5 concentrations, the mean area under the curve (AUC 0.898) suggests that annexin A5 is a favorable marker for AD. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22427","type":"journal-article","created":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T23:30:05Z","timestamp":1275003005000},"page":"2682-2692","source":"Crossref","is-referenced-by-count":21,"title":["Investigation of annexin A5 as a biomarker for Alzheimer's disease using neuronal cell culture and mouse model"],"prefix":"10.1002","volume":"88","author":[{"given":"Mami","family":"Yamaguchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Kokai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin\u2010Ichi","family":"Imai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumiko","family":"Utsumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoichi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirohito","family":"Honda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Mizue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Momma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsu","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shozo","family":"Toyomasu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichi M.","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seijyu","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eri","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshikazu","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Sohma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,7,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/3.4.349"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90974-7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi900608m"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.10.1.78"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)52272-9"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22317"},{"key":"e_1_2_6_8_1","first-page":"640","article-title":"Alteration of annexin expression in pathological neuronal glial reactions. 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