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Authors & Affiliations
Esmin Unaran, Olamide Adebiyi, Amr Eed, Medha Krishnan, Tim Bussey, Lisa Saksida, Ravi S. Menon
Abstract
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by distinct pathologies, including extracellular amyloid beta (AB) deposition and intracellular tau burden. Functional connectivity (FC), the correlation of neuronal signalling between different brain regions, is often impaired in neurological diseases, including AD. Our research focused on investigating the impact of AB pathology on FC using a murine model. We utilized the APP-NLGF (APPKI3) mice as our AD model and compared them with APP-NL (APPKI1) mice as controls. We examined FC changes at two time points: 3 months old (session 1), representing initial plaque deposition, and 7 months old (session 2), representing plaque density saturation.To investigate the alterations between two time points within groups, we conducted resting state functional magnetic imaging (rsfMRI) at 9.4 T and performed paired t-tests on correlation values of resting state timeseries between different brain regions. This comparison revealed no change in APPKI1 group between time points as expected. However, in the APPKI3 group, we observed an increase in interhemispheric FC in the CA1 region of the hippocampus in session 2. To further investigate the alterations between groups within sessions, we performed unpaired t-tests on the correlation values. This investigation revealed that FC between CA1, dentate gyrus (DG) and CA2+CA3 (grouped together) was impaired at 3-months in KI3 relative to KI1, suggesting a loss in FC between hippocampal subfields at this earlier time point. These results align with previous human literature, suggesting that APP-NLGF is a suitable AD model to study FC.