{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:03:43Z","timestamp":1791929023740,"version":"4.3.4"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T00:00:00Z","timestamp":1547424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer\u2019s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-l-methionine (SAM), the principal methyl donor. A common mutation (1364T\/T) of the cystathionine-\u03b3-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the transsulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia\u2014a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B12 (methylcobalamin), vitamin B9 (folic acid), vitamin B6 (pyridoxine), and SAM to patients in early stages of LOAD.<\/jats:p>","DOI":"10.3390\/ijms20020319","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T12:20:07Z","timestamp":1547468407000},"page":"319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Epigenetic Factors in Late-Onset Alzheimer\u2019s Disease: MTHFR and CTH Gene Polymorphisms, Metabolic Transsulfuration and Methylation Pathways, and B Vitamins"],"prefix":"10.3390","volume":"20","author":[{"given":"Gustavo C.","family":"Rom\u00e1n","sequence":"first","affiliation":[{"name":"Department of Neurology, Methodist Neurological Institute, Institute for Academic Medicine Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"Weill Cornell Medical College, Department of Neurology, Cornell University, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0335-8983","authenticated-orcid":false,"given":"Oscar","family":"Mancera-P\u00e1ez","sequence":"additional","affiliation":[{"name":"Universidad Nacional de Colombia, Hospital Universitario Nacional, Faculty of Medicine, Department of Neurology, Bogot\u00e1 ZC 57, Colombia"},{"name":"David Cabello International Alzheimer Disease Scholarship Fund, Houston Methodist Hospital, Houston, TX77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Bernal","sequence":"additional","affiliation":[{"name":"Universidad Nacional de Colombia, Hospital Universitario Nacional, Faculty of Medicine, Department of Neurology, Bogot\u00e1 ZC 57, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/jnc.14148","article-title":"Epigenetics and DNA methylomic profiling in Alzheimer\u2019s disease and other neurodegenerative diseases","volume":"143","author":"Roubroeks","year":"2017","journal-title":"J. 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