{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:52:07Z","timestamp":1781934727163,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T00:00:00Z","timestamp":1275436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG\u201022512"],"award-info":[{"award-number":["AG\u201022512"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hyperhomocysteine (HHcy) is a risk factor for developing Alzheimer's disease (AD). Previously, we showed that diet\u2010induced HHcy accelerated the AD\u2010like phenotype of a transgenic mouse model,\n                    <jats:italic>i.e<\/jats:italic>\n                    ., Tg2576. In the present work, we tested whether an HHcy\u2010lowering strategy in this model would be beneficial. Tg2576 mice received methionine\u2010rich or regular chow diet for 5 mo. Next, while the chow control group was kept on the same regimen, the other mice were randomized into two groups: one was kept on the methionine\u2010rich diet (Met On), the other switched to chow (Met Off). Compared with controls, 5 mo on the methionine\u2010rich diet resulted in HHcy (plasma Hcy level, treated: 12.7\u00b11.2 \u00b5M\n                    <jats:italic>vs<\/jats:italic>\n                    . control: 3.1\u00b10.4 \u00b5M) and significant behavioral impairments (% freezing, treated: 2.4\u00b11.4%\n                    <jats:italic>vs<\/jats:italic>\n                    . control: 19.9\u00b16.9%). At the end of the study, while the Met On group kept Hcy level elevated, the Met Off group had these values indistinguishable from the controls. The reduction in Hcy levels resulted in a significant improvement of the fear\u2010conditioning performance, and an amelioration of the brain amyloidosis. Our results demonstrate that lowering HHcy in a transgenic AD\u2010mouse model is beneficial since it significantly improves behavior deficits and brain amyloidosis. Our findings provide new biological insights for future clinical trials aimed at lowering this modifiable risk factor in human AD.\u2014Zhuo, J.\u2010M., Pratico, D. Normalization of hyperhomocysteinemia improves cognitive deficits and ameliorates brain amyloidosis of a transgenic mouse model of Alzheimer's disease.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    24, 3895\u20133902 (2010).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-161828","type":"journal-article","created":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T22:58:48Z","timestamp":1275519528000},"page":"3895-3902","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Normalization of hyperhomocysteinemia improves cognitive deficits and ameliorates brain amyloidosis of a transgenic mouse model of Alzheimer's disease"],"prefix":"10.1096","volume":"24","author":[{"given":"Jia\u2010Min","family":"Zhuo","sequence":"first","affiliation":[{"name":"Department of Pharmacology Temple University School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Pratic\u00f2","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Temple University School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,6,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(03)00438-1"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.55.11.1449"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020050094"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/73.5.927"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011613"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2006-9404"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.3233\/JAD-2010-1311","article-title":"Reduced homocysteine\u2010thiolactonase activity in Alzheimer's disease","volume":"19","author":"Suszynska J.","year":"2010","journal-title":"J. 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