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Current treatments for AD are inadequate, and there is a need to design preventive strategies that would improve the resistance or resilience to AD pathology. Because aberrant brain DNA methylation (DNAm) is associated with hallmarks of AD, we tested the hypothesis that a nutritional approach using choline, an essential nutrient and methyl donor, would modulate DNAm to ameliorate AD pathologies. Previous studies showed that perinatal choline supplementation (PCS) reduced AD\u2010like neuropathology and inflammation while improving cognitive performance in AD mouse models. Here we investigated hippocampal and cerebral cortical DNAm patterns by reduced representation bisulfite sequencing from 3 to 12\u2009months in wild\u2010type (WT) and\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    AD model mice fed a 1.1\u2009g\/kg control or 5.5\u2009g\/kg PCS diet from conception to weaning.\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    mice showed extensive CpG DNAm changes, which were associated with the age\u2010dependent progression of amyloidosis. PCS induced genotype\u2010specific DNAm patterns and reversed DNAm changes in multiple genes in\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    mice. By associating DNAm with matched transcriptomics, we found that DNAm in\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    mice correlated with the expression of microglial genes, while DNAm\u2010associated genes modulated by PCS were related to synaptic function. Moreover, we found that methylation levels of several CpGs were associated with levels of beta amyloidosis, relating epigenetic changes to neuropathology. Overall, our data suggest that DNAm in the brain serves as an epigenetic mechanism for abnormal gene expression in A\n                    <jats:italic>pp<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    mice and indicate that PCS may promote resilience to synaptic dysfunction through modulating DNAm.\n                  <\/jats:p>","DOI":"10.1111\/acel.70241","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:57:13Z","timestamp":1760407033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Brain\n                    <scp>DNA<\/scp>\n                    Methylation Atlas of\n                    <i>\n                      App\n                      <sup>NL\u2010G\u2010F<\/sup>\n                    <\/i>\n                    Alzheimer's Disease Model Mice Across Age and Region Reveals Choline\u2010Induced Resilience"],"prefix":"10.1111","volume":"24","author":[{"given":"Andre","family":"Krunic","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"},{"name":"Department of Pharmacology, Physiology, and Biophysics Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Bellio","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Z.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Labadorf","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"},{"name":"Bioinformatics Program Boston University  Boston Massachusetts USA"},{"name":"VA Boston Healthcare System  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor D.","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"},{"name":"VA Boston Healthcare System  Boston Massachusetts USA"},{"name":"VA\u00a0Bedford Healthcare System  Boston Massachusetts USA"},{"name":"Boston University Alzheimer's Disease Research Center Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3043-3942","authenticated-orcid":false,"given":"Honghuang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Massachusetts Chan Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany J.","family":"Mellott","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8438-3122","authenticated-orcid":false,"given":"Jan K.","family":"Blusztajn","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"},{"name":"Boston University Alzheimer's Disease Research Center Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"2025.2025 Alzheimer's Disease Facts and 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