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Collapsin response mediator protein 2 (CRMP2), a microtubule (MT)-binding protein, regulates MT dynamics and is phosphorylated at Ser522 by cyclin-dependent kinase 5. Previous studies have shown increased CRMP2 phosphorylation at Ser522 (CRMP2-pSer522) in early AD stages and AD mouse models, where it colocalizes with phosphorylated tau. However, the role of CRMP-pSer522 in AD pathology remains unclear. In this study, we generated double transgenic mice by crossing tau Tg (PS19) mice and CRMP2 S522A knock-in (CRMP2KI) mice, in which S522 of CRMP2 was replaced with alanine to create a phospho-defective model. No significant change in tau phosphorylation was observed in the hippocampus of tau Tg; CRMP2KI mice compared to tau Tg littermates. However, when A\u03b225-35 oligomers were injected into the hippocampus, tau phosphorylation was significantly reduced in A\u03b2-injected tau Tg; CRMP2KI mice compared to A\u03b2-injected tau Tg controls. These findings suggest that CRMP2 phosphorylation at Ser522 promotes A\u03b2-induced tau phosphorylation in this mouse model of AD.<\/jats:p>","DOI":"10.1007\/s12035-025-04721-y","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T12:13:48Z","timestamp":1738412028000},"page":"7413-7420","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Involvement of CRMP2 Phosphorylation in Amyloid Beta-induced Tau Phosphorylation of Hippocampal Neurons in Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.1007","volume":"62","author":[{"given":"Daisuke","family":"Noguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Watamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyu","family":"Nikkuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi C.","family":"Saido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Goshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Ohshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,1]]},"reference":[{"key":"4721_CR1","first-page":"39","volume":"12","author":"B Aghaji","year":"2007","unstructured":"Aghaji B (2007) Alzheimer\u2019s disease \u2013 a review. 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