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Here, to examine the relationship between AD and CVDs, we investigated the changes in heart function in triple\u2010transgenic late\u2010stage AD model mice (3\u00d7 Tg\u2010AD; APPSwe, PS1M146V, and tauP301L). We fed the AD mice folic acid (FA) or folinic acid (FN) and analyzed the protective effects of the compounds on the heart; specifically, 20\u2010month\u2010old triple\u2010transgenic AD mice, weighing 34\u201355\u2009g, were randomly allocated into three groups\u2014the AD, AD\u2009+\u2009FA, and AD\u2009+\u2009FN groups\u2014and subject to gastric feeding with FA or FN once daily at 12\u2009mg\/kg body weight (BW) for 3\u2009months. Mouse BWs were assessed throughout the trial, at the end of which the animals were sacrificed using carbon dioxide suffocation. We found that BW, whole\u2010heart weight, and left\u2010ventricle weight were reduced in the AD\u2009+\u2009FA and AD\u2009+\u2009FN groups as compared with the measurements in the AD group. Furthermore, western blotting of excised heart tissue revealed that the levels of the hypertrophy\u2010related protein markers phospho(p)\u2010p38 and p\u2010c\u2010Jun were markedly decreased in the AD\u2009+\u2009FA group, whereas p\u2010GATA4, and ANP were strongly reduced in the AD\u2009+\u2009FN group. Moreover, the fibrosis\u2010related proteins uPA, MMP\u20102, MEK1\/2 and SP\u20101 were decreased in the heart in both AD\u2009+\u2009FN group. In summary, our results indicate that FA and FN can exert anti\u2010cardiac hypertrophy and fibrosis effects to protect the heart in aged triple\u2010transgenic AD model mice, particular in FN.<\/jats:p>","DOI":"10.1002\/tox.23521","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T09:18:58Z","timestamp":1647249538000},"page":"1740-1749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Edible folic acid and medicinal folinic acid produce cardioprotective effects in late\u2010stage triple\u2010transgenic Alzheimer's disease model mice by suppressing cardiac hypertrophy and fibrosis"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2347-0411","authenticated-orcid":false,"given":"Chih\u2010Yang","family":"Huang","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences China Medical University  Taichung Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital China Medical University  Taichung Taiwan"},{"name":"Department of Biotechnology Asia University  Taichung Taiwan"},{"name":"Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"},{"name":"Center of General Education, Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chen","family":"Su","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010You","family":"Lu","sequence":"additional","affiliation":[{"name":"Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping\u2010Ling","family":"Chiu","sequence":"additional","affiliation":[{"name":"Ept Douliu Chinese Medical Clinic  Douliu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung\u2010Ming","family":"Chang","sequence":"additional","affiliation":[{"name":"1PT Biotechnology Co., Ltd.  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