{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:18:54Z","timestamp":1792145934065,"version":"4.4.0"},"reference-count":0,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2013,1,21]],"date-time":"2013-01-21T00:00:00Z","timestamp":1358726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2013,1,21]]},"abstract":"<jats:p>Hyperhomocysteinemia is associated with Alzheimer's disease (AD). The causality of this association is controversial. In this study we tested the effect of a hyperhomocysteinemia-inducing diet in the ArcA\u03b2 transgenic AD mouse model. At 14 months of age, the hyperhomocysteinemia-inducing diet yielded higher plasma homocysteine levels in ArcA\u03b2 mice compared with wild-type mice. Levels of plasma 5-methyltetrahydrofolate (5-MTHF) in 14-month-old mice on hyperhomocysteinemia-inducing diet were lower in the transgenic than in the wild-type mice. The folate derivate 5-MTHF serves as cofactor in homocysteine metabolism. Oxidative stress, which occurs in the course of disease in the ArcA\u03b2 mice, consumes 5-MTHF. Thus, the transgenic mice may plausibly be more vulnerable to 5-MTHF-depleting effects of hyperhomocysteinemia and more vulnerable to hyperhomocysteinemia-inducing diet. This argues that AD pathology predisposes to hyperhomocysteinemia, i.e., as a facultative consequence of AD. However, we also observed that dietary-induced folate reduction and homocysteine increase was associated with an increase of plasma (young animals) and brain (older animals) amyloid-\u03b2 concentrations. This suggests that the hyperhomocysteinemia-inducing diet worsened pathology in the transgenic mice. In conclusion, this data may argue that folate reduction and hyperhomocysteinemia may contribute to neurodegeneration and may also be triggered by neurodegenerative processes, i.e., represent both a cause and a consequence of neurodegeneration. Such a vicious cycle may be breakable by dietary or supplementation strategies increasing the availability of 5-MTHF.<\/jats:p>","DOI":"10.3233\/jad-2012-121378","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T05:54:17Z","timestamp":1528091657000},"page":"1097-1104","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Hyperhomocysteinemia in Alzheimer's Disease: The Hen and the Egg?"],"prefix":"10.1177","volume":"33","author":[{"given":"Melinda","family":"Farkas","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salla","family":"Keskitalo","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree E.C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Bain","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Semmler","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Ineichen","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvo","family":"Smulders","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luka","family":"Kulic","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Zurich, Zurich, Switzerland"},{"name":"Department of Psychiatry, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Linnebank","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,1,21]]},"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-2012-121378","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-2012-121378","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:01:57Z","timestamp":1777370517000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-2012-121378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,21]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,1,21]]}},"alternative-id":["10.3233\/JAD-2012-121378"],"URL":"https:\/\/doi.org\/10.3233\/jad-2012-121378","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,21]]}}}