{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:10:19Z","timestamp":1777396219764,"version":"3.51.4"},"reference-count":67,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2023,6,27]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Prior research supports a strong link between Alzheimer\u2019s disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-\u03b2 (A\u03b2) is an early biomarker for AD-associated cognitive decline that contributes to concurrent glutamatergic and metabolic dyshomeostasis in humans and male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal glutamatergic activity may impact glucose regulation in an amyloidogenic mouse model. Previous studies have illustrated increased glucose uptake and metabolism using a neuroprotective glutamate modulator (riluzole), supporting the link between glucose and glutamatergic homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We hypothesized that targeting early glutamatergic hyperexcitation through riluzole treatment could aid in attenuating co-occurring metabolic and amyloidogenic pathologies with the intent of ameliorating cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We conducted an early intervention study in male and female transgenic (A\u03b2PP\/PS1) and knock-in (APP\n                      <jats:sup>NL\u00a0-\u00a0F\/NL\u00a0-\u00a0F<\/jats:sup>\n                      ) AD mice to assess the on- and off-treatment effects of prodromal glutamatergic modulation (2\u20136 months of age) on glucose homeostasis and spatial cognition through riluzole treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Results indicated a sex- and genotype-specific effect on glucose homeostasis and spatial cognition with riluzole intervention that evolved with disease progression and time since treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings support the interconnected nature of glucose and glutamatergic homeostasis with amyloid pathology and petition for further investigation into the targeting of this relationship to improve cognitive performance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-221245","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T13:24:12Z","timestamp":1685107452000},"page":"371-392","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Prodromal Glutamatergic Modulation with Riluzole Impacts Glucose Homeostasis and Spatial Cognition in Alzheimer\u2019s Disease Mice"],"prefix":"10.1177","volume":"94","author":[{"given":"Caleigh A.","family":"Findley","sequence":"first","affiliation":[{"name":"Neuroscience Institute, Dale and Deborah Smith Center for Alzheimer\u2019s Research and Treatment, Department of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA"},{"name":"Departments of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel 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