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Magnetic resonance microscopy maps widespread effects of Alzheimer's disease on brain structures and behavior in mice.

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Title: Magnetic resonance microscopy maps widespread effects of Alzheimer's disease on brain structures and behavior in mice.
Authors: Tian, Yuqi (AUTHOR), Hornburg, Kathryn (AUTHOR), Austin, Wyatt (AUTHOR), Cook, James J. (AUTHOR), Qi, Yi (AUTHOR), White, Leonard E. (AUTHOR), Killmar, John T. (AUTHOR), Kaczorowski, Catherine C. (AUTHOR), Ashbrook, David G. (AUTHOR), Johnson, G. Allan (AUTHOR), Williams, Robert W. (AUTHOR)
Source: Nature Neuroscience. Apr2026, Vol. 29 Issue 4, p1007-1020. 14p.
Abstract: Alzheimer's disease has widespread effects on brain structure, function and behavior, but we lack a systematic dissection of its impact across hundreds of forebrain and brainstem regions. Here, using diffusion tensor MRI at 25 µm, we mapped the global consequences of mutations in APP and PSEN1 across 231 regions of interest (ROIs) in male and female 5×FAD BXD hybrid mice at 14 months. Over half of the ROIs change in volume along rostrocaudal and mediolateral axes of the CNS, with unexpected swelling in the neocortex, hippocampus and amygdala of up to 10%, counterbalanced by shrinkage in the thalamus, brainstem and most white matter tracts. Yet, total brain volume is unaltered. Variation in individual ROI volumes is highest in females. Differences in fear acquisition and contextual memory performance covary with volumes of several regions and can have opposite polarities between cases and controls. These structural benchmarks establish a foundation for testing therapeutic interventions in preclinical trials. Alzheimer's disease alters brain structure broadly, but its regional impact is poorly mapped. Here, the authors show that App and Psen1 mutations in mice cause volume changes across 231 regions, which are associated with individual differences in behavior. [ABSTRACT FROM AUTHOR]
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Database: Psychology and Behavioral Sciences Collection
Description
Abstract:Alzheimer's disease has widespread effects on brain structure, function and behavior, but we lack a systematic dissection of its impact across hundreds of forebrain and brainstem regions. Here, using diffusion tensor MRI at 25 µm, we mapped the global consequences of mutations in APP and PSEN1 across 231 regions of interest (ROIs) in male and female 5×FAD BXD hybrid mice at 14 months. Over half of the ROIs change in volume along rostrocaudal and mediolateral axes of the CNS, with unexpected swelling in the neocortex, hippocampus and amygdala of up to 10%, counterbalanced by shrinkage in the thalamus, brainstem and most white matter tracts. Yet, total brain volume is unaltered. Variation in individual ROI volumes is highest in females. Differences in fear acquisition and contextual memory performance covary with volumes of several regions and can have opposite polarities between cases and controls. These structural benchmarks establish a foundation for testing therapeutic interventions in preclinical trials. Alzheimer's disease alters brain structure broadly, but its regional impact is poorly mapped. Here, the authors show that App and Psen1 mutations in mice cause volume changes across 231 regions, which are associated with individual differences in behavior. [ABSTRACT FROM AUTHOR]
ISSN:10976256
DOI:10.1038/s41593-025-02199-4