{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:05:22Z","timestamp":1782230722904,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,2,10]],"date-time":"2012-02-10T00:00:00Z","timestamp":1328832000000},"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":[[2012,4]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic> (2012) <jats:bold>121<\/jats:bold>, 135\u2013145.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Although the pathological role of presenilin\u20101 mutation in early onset familial Alzheimer\u2019s disease has been widely studied, few focused on how the presenilin\u20101 mutations result in memory impairment and tau hyperphosphorylation. In the present study, we expressed human Val97Leu mutant presenilin\u20101, which is reported in Chinese pedigrees by our group, in transgenic mice and found that the mutant presenilin\u20101 induced spatial memory deficit and tau hyperphosphorylation at PHF\u20101, pS199\/202, pT231 and pS396 epitopes, but not at pS214 and pS422 epitopes. Pearson analysis showed that the memory deficit was only significantly correlated with tau phosphorylation level at PHF\u20101, pS199\/202, pT231 and pS396 epitopes. Additionally, the hyperphosphorylated tau and tangle\u2010like argentophilic structures were detected at CA3 and CA4, but not CA1, region of hippocampus, and we also found tangle\u2010like structure and wizened degenerative neurons in frontal cortex. We demonstrated the tau hyperphosphorylation at the same epitopes in N2a cells expressing the mutant presenilin\u20101, which is caused by inhibition of phosphoinositol\u20103 kinase\/Akt and activation of glycogen synthase kinase\u20103 specifically. Our data demonstrated that human Val97Leu mutant presenilin\u20101 causes spatial memory deficit in mice and increases tau phosphorylation level in glycogen synthase kinase\u20103\u2010dependent manner.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2011.07489.x","type":"journal-article","created":{"date-parts":[[2011,9,20]],"date-time":"2011-09-20T11:34:17Z","timestamp":1316518457000},"page":"135-145","source":"Crossref","is-referenced-by-count":19,"title":["Val97Leu mutant presenilin\u20101 induces tau hyperphosphorylation and spatial memory deficit in mice and the underlying mechanisms"],"prefix":"10.1111","volume":"121","author":[{"given":"Yue","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.041603398"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600251"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4067-07.2008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00942-9"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21601"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100710200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20083"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.11.019"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/383710a0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.06.072"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402733101"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/373523a0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(01)00011-9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.13.4913"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/4789"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507326200"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021691918517"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00242-5"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3233\/JAD-2005-7204","article-title":"One novel presenilin\u20101 gene mutation in a Chinese pedigree of familial Alzheimer\u2019s disease","volume":"7","author":"Jia J.","year":"2005","journal-title":"J. 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