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Behavioral assessments included locomotor activity and hippocampal-dependent spatial learning and memory. Amyloid burden, lipid peroxidation, peripheral metabolic, and inflammatory markers, and hippocampal microglial phenotypes were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      D-Met did not alter locomotor or exploratory behavior but improved spatial memory recall in both sexes of APP\/PS1 mice and in female APP\n                      <jats:sup>NL\u2212F<\/jats:sup>\n                      mice. APP\n                      <jats:sup>NL\u2212F<\/jats:sup>\n                      males exhibited improved Morris water maze learning. Amyloid pathology was region-specifically reduced, including decreased hippocampal plaque size in male APP\n                      <jats:sup>NL\u2212F<\/jats:sup>\n                      mice, reduced cortical plaque size in female APP\/PS1 mice, and lower soluble amyloid-\u03b2 (A\u03b2)\n                      <jats:sub>42<\/jats:sub>\n                      in male APP\/PS1 mice. Lipid peroxidation was reduced only in female APP\n                      <jats:sup>NL\u2212F<\/jats:sup>\n                      mice. D-Met induced pronounced sex-dependent peripheral effects, increasing adiposity and pro-inflammatory adipose signaling in males, while reducing perigonadal white adipose tissue IL-6 expression in female APP\n                      <jats:sup>NL\u2212F<\/jats:sup>\n                      mice. In the hippocampus, D-Met decreased microglial activation, with female APP\n                      <jats:sup>NL\u2212F<\/jats:sup>\n                      mice showing reduced Iba1 and disease-associated microglial markers and increased Axl expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Short-term D-Met acts as a metabolic and redox modulator with amyloid-lowering effects mediated by improved microglial function. Therapeutic efficacy is strongly sex- and model-dependent, with the greatest benefit observed in female APP\n                      <jats:sup>NL\u2212F<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261444307","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:28:13Z","timestamp":1776954493000},"page":"1807-1819","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["D-methionine improves spatial navigation and attenuates oxidative stress and amyloid pathology in a sex-specific manner"],"prefix":"10.1177","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2611-1150","authenticated-orcid":false,"given":"Mackenzie R.","family":"Peck","sequence":"first","affiliation":[{"name":"Southern Illinois University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenelle E.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Southern Illinois University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7995-842X","authenticated-orcid":false,"given":"Tiarra","family":"Hill","sequence":"additional","affiliation":[{"name":"Southern Illinois University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Quinn","sequence":"additional","affiliation":[{"name":"Southern Illinois University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erol D.","family":"Ikiz","sequence":"additional","affiliation":[{"name":"Southern Illinois University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-876X","authenticated-orcid":false,"given":"Angel","family":"Lopez","sequence":"additional","affiliation":[{"name":"Southern Illinois University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1037-0809","authenticated-orcid":false,"given":"Erin R.","family":"Hascup","sequence":"additional","affiliation":[{"name":"Southern Illinois University School of Medicine"},{"name":"Southern Illinois University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chilman","family":"Bae","sequence":"additional","affiliation":[{"name":"Southern Illinois University Carbondale"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6604-1874","authenticated-orcid":false,"given":"Kevin N.","family":"Hascup","sequence":"additional","affiliation":[{"name":"Southern Illinois University School of Medicine"},{"name":"Southern Illinois University School of Medicine"},{"name":"Southern Illinois University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666170720095240"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-025-01162-y"},{"key":"e_1_3_3_4_2","article-title":"Reducing microglial lipid load enhances \u03b2 amyloid phagocytosis in an Alzheimer\u2019s disease mouse model","volume":"11","author":"Wu X","year":"2025","unstructured":"Wu X, Miller JA, Lee BTK, et al. 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