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ABSTRACT Alzheimer's disease (AD) and its associated pathology have 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, we characterized amyloid‐beta (Aβ) and tau lesions in five species of aged felids (n= 9; cheetah, clouded leopard, African lion, serval, Siberian tiger). We performed immunohistochemistry to detect Aβ40 and Aβ42 in plaques and vessels and hyperphosphorylated tau in the temporal lobe gyrus sylvius and in the CA1 and CA3 subfields of the hippocampus. We also quantified the densities and morphological types of microglia expressing IBA1. We found that diffuse Aβ42 plaques, but not dense‐core plaques, were present more frequently in the temporal cortex and tended to be more common than Aβ40 plaques across species. Conversely, vascular Aβ was labeled more consistently with Aβ40 for each species on average. Although all individuals showed some degree of Aβ40 and/or Aβ42 immunoreactivity, only the cheetahs and clouded leopards exhibited intraneuronal hyperphosphorylated tau (i.e., pretangles), which was more common in the hippocampus. Reactive, intermediate microglia were significantly associated with total Aβ40 vessel area and pretangle load in the hippocampus. This study demonstrates the co‐occurrence of Aβ and tau pathology in two felid species, cheetahs and clouded leopards. Overall, these results provide an initial view of the manifestation of Aβ and tau pathology in aged, large‐brained felids, which can be compared with markers of neurodegeneration across different taxa, including domestic cats, nonhuman primates, and humans.
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How genomic insights into the evolutionary history of clouded leopards inform their conservation
Clouded leopards (Neofelisspp.), a morphologically and ecologically distinct lineage of big cats, are severely threatened by habitat loss and fragmentation, targeted hunting, and other human activities. The long-held poor understanding of their genetics and evolution has undermined the effectiveness of conservation actions. Here, we report a comprehensive investigation of the whole genomes, population genetics, and adaptive evolution ofNeofelis. Our results indicate the genusNeofelisarose during the Pleistocene, coinciding with glacial-induced climate changes to the distributions of savannas and rainforests, and signatures of natural selection associated with genes functioning in tooth, pigmentation, and tail development, associated with clouded leopards’ unique adaptations. Our study highlights high-altitude adaptation as the main factor driving nontaxonomic population differentiation inNeofelis nebulosa. Population declines and inbreeding have led to reduced genetic diversity and the accumulation of deleterious variation that likely affect reproduction of clouded leopards, highlighting the urgent need for effective conservation efforts.
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- Award ID(s):
- 1753760
- PAR ID:
- 10474111
- Publisher / Repository:
- AAAS
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 9
- Issue:
- 40
- ISSN:
- 2375-2548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1126/sciadv.adh9143
