{"doi":"10.3233/jad-221245","title":"Prodromal Glutamatergic Modulation with Riluzole Impacts Glucose Homeostasis and Spatial Cognition in Alzheimer’s Disease Mice","abstract":"BACKGROUND: Prior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-β (Aβ) 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. OBJECTIVE: 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. METHODS: We conducted an early intervention study in male and female transgenic (AβPP/PS1) and knock-in (APPNL - F/NL - F) AD mice to assess the on- and off-treatment effects of prodromal glutamatergic modulation (2-6 months of age) on glucose homeostasis and spatial cognition through riluzole treatment. RESULTS: 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. CONCLUSION: 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.","journal":"Journal of Alzheimer s Disease","year":2023,"id":351190,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":371883,"name":"Samuel McFadden","orcid":"0000-0002-2289-5066","position":1,"is_corresponding":false},{"id":855014,"name":"MaKayla F. Cox","orcid":"0000-0002-7625-5339","position":2,"is_corresponding":false},{"id":472099,"name":"Lindsey N. Sime","orcid":"0000-0002-5934-7725","position":3,"is_corresponding":false},{"id":809143,"name":"Mackenzie R. Peck","orcid":"0000-0002-2611-1150","position":4,"is_corresponding":false},{"id":657744,"name":"Kathleen Quinn","orcid":null,"position":5,"is_corresponding":false},{"id":356147,"name":"Andrzej Bartke","orcid":"0000-0002-2569-557X","position":6,"is_corresponding":false},{"id":356149,"name":"Kevin N. Hascup","orcid":"0000-0001-6604-1874","position":7,"is_corresponding":false},{"id":356148,"name":"Erin R. Hascup","orcid":"0000-0003-1037-0809","position":8,"is_corresponding":false},{"id":472098,"name":"Caleigh A. Findley","orcid":"0000-0002-8759-1661","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:12:41.740237Z","pmid":"37248899","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}