{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:32:57Z","timestamp":1789421577277,"version":"build-2803163510"},"reference-count":79,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate\u2010weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high\u2010resolution spatial mapping of cerebral glutamate and investigated subregional changes in a sex\u2010specific manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Eight\u2010month\u2010old male and female AD mice harboring mutant amyloid precursor protein (<jats:italic>APP<\/jats:italic><jats:sup><jats:italic>NL<\/jats:italic>\u2010<jats:italic>F\/NL\u2010F<\/jats:italic><\/jats:sup>: <jats:italic>n<\/jats:italic> = 36) and wild\u2010type (WT: <jats:italic>n<\/jats:italic> = 39) mice underwent GluCEST MRI, followed by proton magnetic resonance spectroscopy (<jats:sup>1<\/jats:sup>H\u2010MRS) in hippocampus and thalamus\/hypothalamus using 9.4T preclinical MR scanner.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>GluCEST measurements revealed significant (<jats:italic>p<\/jats:italic>\u00a0\u2264\u00a00.02) glutamate loss in the entorhinal cortex (% change \u00b1 standard error: 8.73\u00a0\u00b1\u00a02.12%), hippocampus (11.29\u00a0\u00b1\u00a02.41%), and hippocampal fimbriae (19.15\u00a0\u00b1\u00a02.95%) of male AD mice. A similar loss of hippocampal glutamate in male AD mice (11.22\u00a0\u00b1\u00a02.33%; <jats:italic>p<\/jats:italic> = 0.01) was also observed in <jats:sup>1<\/jats:sup>H\u2010MRS.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSIONS<\/jats:title><jats:p>GluCEST MRI detected glutamate reductions in the fimbria and entorhinal cortex of male AD mice, which was not reported previously. Resilience in female AD mice against these changes indicates an intact status of cerebral energy metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p>Glutamate levels were monitored in different brain regions of early\u2010stage Alzheimer's disease (AD) and wild\u2010type male and female mice using glutamate\u2010weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI).<\/jats:p><jats:p>Male AD mice exhibited significant glutamate loss in the hippocampus, entorhinal cortex, and the fimbriae of the hippocampus.<\/jats:p><jats:p>Interestingly, female AD mice did not have any glutamate loss in any brain region and should be investigated further to find the probable cause.<\/jats:p><jats:p>These findings demonstrate previously unreported sex\u2010specific glutamate changes in hippocampal sub\u2010regions using high\u2010resolution GluCEST MRI.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14190","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T06:32:40Z","timestamp":1726122760000},"page":"7124-7137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Detection of sex\u2010specific glutamate changes in subregions of hippocampus in an early\u2010stage Alzheimer's disease mouse model using GluCEST MRI"],"prefix":"10.1002","volume":"20","author":[{"given":"Narayan Datt","family":"Soni","sequence":"first","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine Center for Advanced Metabolic Imaging in Precision Medicine University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshuman","family":"Swain","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine Center for Advanced Metabolic Imaging 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