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Age-Related Pathology and Microglial Activation in Felid Brains

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Alzheimer’s disease (AD) and associated pathology has been primarily identified in humans, who have relatively large brains and long lifespans. To expand what is known about aging and neurodegeneration across mammalian species, I characterized amyloid-beta (Aβ) and tau pathologies in aged felids (n=6) of five different species (cheetah, clouded leopard, African lion, serval, Siberian tiger), most of which have not previously been studied. Diffuse Aβ42 plaques, but not dense-core plaques, were present in the cerebral cortex, and tended to be more common than Aβ40 plaques across species. The opposite was observed with vascular Aβ, with more Aβ40 vessels than Aβ42 vessels per species, on average. Although all individuals showed some degree of Aβ40 and/or Aβ42 immunoreactivity (primarily in the cerebral cortex), only the cheetah and the two clouded leopards had tau pathology, which was observed exclusively in the form of pretangles in the hippocampus. This study demonstrates the co-occurrence of Aβ and tau pathology in these two felid species. I also found that activated, intermediate hippocampal microglia were significantly associated with pretangle load in the three individuals that possessed tau pathology. Overall, these results provide an initial view of the manifestation of age-related brain pathology in these large-brained felids, which can be compared with neurodegeneration across different taxa, including domestic cats, nonhuman primates, and humans.

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