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Abstract #0828

Simultaneous WF-Ca2+ and BOLD-fMRI reveals modality-specific and sex-based differences in prodromal Alzheimer’s disease

Francesca Mandino1, Xilin Shen1, Carolyn A Fredericks2, Stephen M Strittmatter2,3,4,5,6, and Evelyn MR Lake1,4,7
1Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States, 2Neurology, Yale School of Medicine, New Haven, CT, United States, 3Cellular Neuroscience, Yale School of Medicine, New Haven, CT, United States, 4Wu Tsai Institute, Yale School of Medicine, New Haven, CT, United States, 5Kavli Institute of Neuroscience, Yale School of Medicine, New Haven, CT, United States, 6Neuroscience, Yale School of Medicine, New Haven, CT, United States, 7Biomedical Engineering, Yale School of Medicine, New Haven, CT, United States

Synopsis

Keywords: Small Animals, Alzheimer's Disease, Sex-based differences

Motivation: This work lays a foundation for studying sex-specific network dysfunction in prodromal AD with multiple contrasts.

Goal(s): Sex-, mode-, time-, and group- (AD vs. control) based differences in connectivity were quantified.

Approach: Male and female wild-type (WT) and AD mice were imaged at 4 and 6 months-of-age (M), paralleling young adulthood in humans.

Results: Simultaneous wide-field fluorescent calcium (WF-Ca2+) and BOLD (blood-oxygen-level dependent) functional magnetic resonance imaging (fMRI) reveal modality- and biological sex-specific differences in cortical connectivity during prodromal Alzheimer’s disease (AD). AD-related changes in connectivity emerged earlier in females, was apparent in WF-Ca2+ prior to BOLD-fMRI and showed diverging patterns across modes.

Impact: Relative to men, women face twice the lifetime risk of AD-related cognitive impairment. Causes of this discrepancy are unknown and understudied–especially in animal models. We report a novel dual-imaging framework for studying sex- and AD-related network disruption in mice.

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Abstract

Keywords