Abstract

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.

Document Type

Article

Publication Date

5-15-2024

Notes/Citation Information

Copyright © 2024 the authors

Digital Object Identifier (DOI)

https://doi.org/10.1523/JNEUROSCI.2366-23.2024

Funding Information

The study was supported by National Institutes of Health/National Institute on Aging (NIH/NIA) R01AG056998 (EH/CN/CELS). J.A.N. is supported by NIH/NIA T32AG073088. We thank Christine Lee and Elena Singh for their assistance in quality control of the imaging data.

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