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Regional changes in overall patterns of protein phosphorylation are likely crucial to promote transition from a presymptomatic to a symptomatic state in response to accumulating <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2<jats:sub>42.<\/jats:sub> Here, we used unbiased proteomic approaches to compare the phosphoproteome of presymptomatic and symptomatic <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">CRND<\/jats:styled-content>8 mice and identify network disruptions in signaling pathways implicated in the manifestation of behavioral indices of learning and memory impairment. Phosphopeptide enrichment with triple isotopic dimethylation labeling combined with online multidimensional separation and <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> was used to profile phosphoproteome changes in 2\u2010 and 6\u2010month\u2010old <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">CRND<\/jats:styled-content>8 mice and congenic littermate controls. We identified 1026 phosphopeptides representing 1168 phosphorylation sites from 476 unique proteins. Of these, 595 phosphopeptides from 293 unique proteins were reliably quantified and 139 phosphopeptides were found to change significantly in the hippocampus of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">CRND<\/jats:styled-content>8 mice following conversion from a presymptomatic to a symptomatic state.<\/jats:p>","DOI":"10.1002\/pmic.201200415","type":"journal-article","created":{"date-parts":[[2013,1,18]],"date-time":"2013-01-18T04:22:48Z","timestamp":1358482968000},"page":"1292-1305","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Phosphoproteome analysis of an early onset mouse model (<scp>T<\/scp>g<scp>CRND<\/scp>8) of <scp>A<\/scp>lzheimer's disease reveals temporal changes in neuronal and glia signaling pathways"],"prefix":"10.1002","volume":"13","author":[{"given":"Fangjun","family":"Wang","sequence":"first","affiliation":[{"name":"Key Lab of Separation Sciences for Analytical Chemistry National Chromatographic R &amp; A Center Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian P. 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