biostudies-literatureFindley CANIA NIH HHSKenneth Stark EndowmentNational Institute on AgingDale and Deborah Smith Center for Alzheimer’s Research and Treatment491-505https://www.ebi.ac.uk/biostudies/studies/S-EPMC11639043biostudies-literatureUnknown102(2)<h4>Background</h4>It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes.<h4>Objective</h4>In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP^NL-F/NL--F).<h4>Methods</h4>At 2-4 and 18+ months old, male and female APP^NL/NL, APP^NL-F/NL-F, and C57BL/6 mice underwent cognitive assessment using Morris water maze (MWM) and Novel Object Recognition (NOR). Then, basal and 70 mM KCl stimulus-evoked glutamate release was measured in the dentate gyrus (DG), CA3, and CA1 regions of the hippoJournal of Alzheimer's disease : JADSexual dimorphism, altered hippocampal glutamatergic neurotransmission, and cognitive impairment in APP knock-in mice.PMC11639043R01 AG057767R01 AG061937R01AG061937R01AG057767Hill TPeck MRHascup ERMcFadden SAQuinn KFindley CAHascup KNfalseSexual dimorphism, altered hippocampal glutamatergic neurotransmission, and cognitive impairment in APP knock-in mice.<h4>Background</h4>It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes.<h4>Objective</h4>In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP^NL-F/NL--F).<h4>Methods</h4>At 2-4 and 18+ months old, male and female APP^NL/NL, APP^NL-F/NL-F, and C57BL/6 mice underwent cognitive assessment using Morris water maze (MWM) and Novel Object Recognition (NOR). Then, basal and 70 mM KCl stimulus-evoked glutamate release was measured in the dentate gyrus (DG), CA3, and CA1 regions of the hippo2024-01-01T00:00:00Z2024 Nov2026-05-18T03:18:53.443Z2026-05-18T03:13:01.628ZS-EPMC116390433954398510.3233/JAD-24079510.3233/jad-240795