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The impact of A\u03b2 active\nvaccines on epigenetic markers has not been studied thus far.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective:<\/jats:title>\n<jats:p>The current study aims to establish the relationship between active immunotherapy with a\nMER5101-based vaccine (consisting of A\u03b21-15 copies conjugated with a 7 aa spacer to the diphtheria\ntoxoid carrier protein, formulated in a Th2-biased adjuvant) and epigenetic DNA modifications in the\nhippocampus of APPswe\/PS1dE9 mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>As we previously reported, immunotherapy started when the mice were 10 months of age and\nbehavioral testing occurred at 14 months of age, after which the mice were sacrificed for further analysis\nof their brains. In this add-on study, global levels of DNA methylation and hydroxymethylation, and\nDNA methyltransferase 3A (DNMT3A) were determined using quantitative immunohistochemistry, and\ncompared to our previously analyzed immunization-induced changes in AD-related neuropathology and\ncognition.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>Active immunization did not affect global DNA methylation levels but instead, resulted in decreased\nDNA hydroxymethylation and DNMT3A levels. Independent of immunization, inverse correlations\nwith behavioral performance were observed for levels of DNA methylation and hydroxymethylation,\nas well as DNMT3A, while A\u03b2 pathology and synaptic markers did not correlate with DNA methylation\nlevels but did positively correlate with DNA hydroxymethylation and levels of DNMT3A.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>Our results indicate that active A\u03b2 vaccination has significant effects on the epigenome in\nthe hippocampus of APPswe\/PS1dE9 mice, and suggest that DNA methylation and hydroxymethylation\nmay be involved in cognitive functioning.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1567205016666190827122009","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T10:49:20Z","timestamp":1566902960000},"page":"861-870","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Active Amyloid-\u03b2 Vaccination Results in Epigenetic Changes in the Hippocampus of an Alzheimer\u2019s Disease-Like Mouse Model"],"prefix":"10.2174","volume":"16","author":[{"given":"Roy","family":"Lardenoije","sequence":"first","affiliation":[{"name":"Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dani\u00ebl L.A.","family":"van den Hove","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht 6200MD, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie E.","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht 6200MD, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Havermans","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht 6200MD, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Mercia Pharma, New York, New York 10036, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart P.F.","family":"Rutten","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht 6200MD, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia A.","family":"Lemere","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/j.jalz.2015.06.1884","volume":"11","author":"Agadjanyan M.G.","unstructured":"Agadjanyan M.G.; Petrovsky N.; Ghochikyan A.; A fresh perspective from immunologists and vaccine researchers: active vaccination strategies to prevent and reverse Alzheimer\u2019s disease. 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