{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:13:08Z","timestamp":1791274388224,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,11,7]],"date-time":"2008-11-07T00:00:00Z","timestamp":1226016000000},"content-version":"vor","delay-in-days":37,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2008,10]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n \n We examined the epistatic effect between haplotypes of\n glycogen synthase kinase<\/jats:italic>\n \u2010\n 3<\/jats:italic>\n \u03b2 (\n GSK3B<\/jats:italic>\n ) gene and\n microtubule<\/jats:italic>\n \u2010\n associated protein Tau<\/jats:italic>\n (\n MAPT<\/jats:italic>\n ) gene in Alzheimer's disease (AD).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A genetic association study of three AD cohorts was made. Linear regression analyses were used to examine effects of\n MAPT<\/jats:italic>\n polymorphisms on gene expression and alternative splicing. \u03b2\u2010Catenin levels and signaling were determined using Western blot and luciferase reporter assays in cells transfected with a combination of\n GSK3B<\/jats:italic>\n and\n MAPT<\/jats:italic>\n complementary DNA.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Consistent interaction between\n GSK3B<\/jats:italic>\n and\n MAPT<\/jats:italic>\n genes in three late\u2010onset AD cohorts was observed, with the\n GSK3B<\/jats:italic>\n haplotype (T\u2010T) significantly increasing the risk for AD in individuals with at least one H2 haplotype (odds ratio, 1.68\u20132.33;\n p<\/jats:italic>\n = 0.005\u20130.036). The\n GSK3B<\/jats:italic>\n haplotype was significantly protective in the Chinese cohort (odds ratio, 0.33;\n p<\/jats:italic>\n = 0.016), after adjusting for the effect of age and sex. There are significant differences in in vivo transcriptional efficiency between the two\n MAPT<\/jats:italic>\n haplotypes (H1 and H2) as determined by measurement of cerebellar transcripts (\n p<\/jats:italic>\n < 0.001). Overexpression of either\n MAPT<\/jats:italic>\n or\n GSK3B<\/jats:italic>\n resulted in decreased \u03b2\u2010catenin levels compared with a control vector (\n p<\/jats:italic>\n < 0.001). Conversely, cotransfection of both of these molecules increased \u03b2\u2010catenin signaling.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n Our genetic and biochemical analyses have identified a novel interaction between Tau and GSK\u20103\u03b2 in late\u2010onset AD causative factors. Our data are consistent with an epistatic model of interaction where discordant levels of\n GSK3B<\/jats:italic>\n and\n MAPT<\/jats:italic>\n gene expression can lead to altered \u03b2\u2010catenin levels and pathogenicity. Ann Neurol 2008\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ana.21476","type":"journal-article","created":{"date-parts":[[2008,11,7]],"date-time":"2008-11-07T16:14:37Z","timestamp":1226074477000},"page":"446-454","source":"Crossref","is-referenced-by-count":63,"title":["Glycogen synthase kinase\u20103\u03b2 and tau genes interact in Alzheimer's disease"],"prefix":"10.1002","volume":"64","author":[{"given":"John B. J.","family":"Kwok","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clement T.","family":"Loy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Hallupp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Anthony","family":"Broe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lovestone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter 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