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Brain glucose hypometabolism is a core hallmark of AD and emerges decades before clinical decline, but accumulating evidence indicates that its causes, timing, and functional consequences differ between women and men. In this review, we synthesize findings from neuroimaging, molecular, and cellular studies to examine how sex\u2010dependent regulation of glucose transport, glycolysis, and mitochondrial function interacts with aging and AD pathology. We highlight reinforcing evidence for a steeper and more pathology\u2010linked decline in mitochondrial glucose metabolism in females, particularly in the context of menopause and apolipoprotein E (\n                    <jats:italic>APOE) \u03b54<\/jats:italic>\n                    genotype. We identify major knowledge gaps at the level of cell type, brain region, and disease stage, and outline priorities for sex\u2010informed, mechanistically anchored research to enable metabolic\u2010precision interventions for AD risk and progression.\n                  <\/jats:p>","DOI":"10.1002\/alz.71491","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T03:29:47Z","timestamp":1781148587000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4902-7688","authenticated-orcid":false,"given":"Marjan","family":"Ramezan","sequence":"first","affiliation":[{"name":"Neurobiology of Nutrition Laboratory Department of Nutritional Sciences College of Health &amp; Human Sciences Texas Tech University  Lubbock Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aphrodite","family":"Demetriou","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Care Sciences and Society Division of Neurogeriatrics Karolinska Institute  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Nicole","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Neuroscience College of Science and BIO5 Institute University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Nalvarte","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Care Sciences and Society Division of Neurogeriatrics Karolinska Institute  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Shin","sequence":"additional","affiliation":[{"name":"Neurobiology of Nutrition Laboratory Department of Nutritional Sciences College of Health &amp; Human Sciences Texas Tech University  Lubbock Texas USA"},{"name":"Human Molecular Aging Center Texas Tech University  Lubbock Texas USA"},{"name":"Center of Excellence for Translational Neuroscience &amp; Therapeutics Texas Tech University Health Sciences Center  Lubbock Texas 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