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The relationship between ovarian hormones and AD has been explored using AD animal models, especially through ovariectomy (OVX) in established AD models. The link between early-stage AD and ovarian hormones, however, remains unclear, largely due to the lack of suitable animal models. Appropriate models for studying early-stage AD pathology, treatment, and prevention are critically needed. The\n                    <jats:italic>App<\/jats:italic>\n                    knock-in mouse model, which carries a single amyloid precursor protein (\n                    <jats:italic>App<\/jats:italic>\n                    ) gene mutation, effectively reproduces early amyloid AD pathology. To elucidate the relationship between ovarian hormone deficiency and the behavioral phenotypes of a preclinical AD model, we applied a comprehensive behavioral test battery to this mouse model with bilateral OVX. The\n                    <jats:italic>App<\/jats:italic>\n                    mutation reduced anxiety-like behavior and impaired performance in the fear memory task. OVX restored the anxiety-like behavior of the\n                    <jats:italic>App<\/jats:italic>\n                    mutation mice to a level comparable to that in wild-type (WT) mice. Furthermore, OVX enhanced performance in a fear memory task in both genotypes and reduced amyloid-\u03b2 staining in WT mice. Together, these findings suggest that OVX attenuates AD-related phenotypes in a preclinical AD model and in C57BL\/6\u00a0J WT mice.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-20006-9","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:03:57Z","timestamp":1761645837000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ovariectomy attenuates phenotypes related to Alzheimer\u2019s disease in a preclinical mouse model and in C57BL\/6 J mice"],"prefix":"10.1038","volume":"15","author":[{"given":"Kazuki","family":"Fujii","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumie","family":"Koshidaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Yanagibashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihiro","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi C.","family":"Saido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Takao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"issue":"4","key":"20006_CR1","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1002\/alz.12638","volume":"18","author":"J Gaugler","year":"2022","unstructured":"Gaugler, J. et al. 2022 Alzheimer\u2019s disease facts and figures. 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