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NFTs also contain Wiskott\u2010Aldrich syndrome protein family verprolin\u2010homologous protein 1 (WAVE1) and collapsin response\u2010mediator protein 2 (CRMP2). Although Cdk5 is known to phosphorylate tau, WAVE1, and CRMP2, the significance of this with respect to NFT formation remains to be elucidated. This study examines the involvement of phosphorylated (p\u2010) CRMP2 and WAVE1 in p\u2010tau aggregates using a triple\u2010transgenic (3\u00d7Tg; APPswe\/PS1M146V\/tauP301L) AD mouse model. First, we verified the colocalization of p\u2010WAVE1 and p\u2010CRMP2 with aggregated hyperphosphorylated tau in the hippocampus at 23 months of age. Biochemical analysis revealed the inclusion of p\u2010WAVE1, p\u2010CRMP2, and tau in the sarkosyl\u2010insoluble fractions of hippocampal homogenates. To test the significance of phosphorylation of these proteins further, we administered all\u2010trans\u2010retinoic acid (ATRA) to the 3\u00d7Tg mice, which downregulates Cdk5 and GSK3\u03b2 activity. In ATRA\u2010treated mice, fewer and smaller tau aggregates were observed compared with non\u2010ATRA\u2010treated mice. These results suggest the possibility of novel therapeutic target molecules for preventing tau pathology. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23674","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T05:47:03Z","timestamp":1443073623000},"page":"15-26","source":"Crossref","is-referenced-by-count":24,"title":["Colocalization of phosphorylated forms of WAVE1, CRMP2, and tau in Alzheimer's disease model mice: Involvement of Cdk5 phosphorylation and the effect of ATRA treatment"],"prefix":"10.1002","volume":"94","author":[{"given":"Naoto","family":"Watamura","sequence":"first","affiliation":[{"name":"Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Toba","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Brain Science, Department of Life Science and 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