DYRK1A protein-kinase overexpression was identified as key player in cognitive impairments observed in Down syndrome (DS) patients and in animal models. Inhibition of this kinase rescued cognitive deficits in the Dp1Yey mouse model of DS, but the associated mechanisms remain unknown. Here we used multimodal brain MRI and characterized the morphology, microstructure and functional connectivity (FC) of Dp1Yey mice. Voxel-based morphometry revealed brain-wide morphological alterations in Dp1Yey mice, while DTI analysis revealed white matter changes. Further, rsfMRI showed that pharmacologic DYRK1A inhibition modifies the functional connectivity for memory related nodes, synergistic with cognitive improvements observed in behavioral tests.
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