Abstract #3914

Longitudinal simultaneous fMRI and mesoscale calcium imaging in a mouse model of Alzheimer’s disease

Francesca Mandino¹, Xilin Shen², Gabriel Desrosiers-Gregoire³, David O'Connor⁴, Bandhan Mukherjee⁵, Kristin DeLuca⁵, Ali Hamodi⁴, Ashley Owens⁵, Yonghyun Ha¹, An Qu¹, John Onofrey⁴, Xenophon Papademetris⁴, Mallar Chakravarty³, Michael C. Crair⁴, Stephen M Strittmatter⁵, and Evelyn Lake¹

¹Radiology, Yale University, New Haven, CT, United States, ²Radiology and bioimaging sciences, Yale University, New Haven, CT, United States, ³Douglas Mental Health University Institute, McGill, Montreal, QC, Canada, ⁴Yale University, New Haven, CT, United States, ⁵Neurology and Neuroscience, Yale University, New Haven, CT, United States

Synopsis

Keywords: Alzheimer's Disease, BrainMultimodal neuroimaging plays an active role in understanding clinically accessible biomarkers of health and disease. Using simultaneous mesoscopic calcium imaging and BOLD-fMRI, we examine spontaneous activity in a GCaMP-positive mouse model of Alzheimer’s disease (AD)—longitudinally—at 4, 6, and 9 months. We find that both imaging modalities show early wide-spread changes in connectivity in AD compared to controls, with diverging trends at 6months. Intriguingly, these neuroimaging changes precede typical behaviour deficits. Further, preliminary evidence of cross-modal uncoupling hints at a complex relationship between excitatory neural activity (calcium imaging data), and the BOLD signal that is affected by AD-related progression.

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