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To expand what is known about aging and neurodegeneration across mammalian species, we characterized amyloid\u2010beta (A\u03b2) and tau lesions in five species of aged felids (\n                    <jats:italic>n<\/jats:italic>\n                    = 9; cheetah, clouded leopard, African lion, serval, Siberian tiger). We performed immunohistochemistry to detect A\u03b240 and A\u03b242 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 A\u03b242 plaques, but not dense\u2010core plaques, were present more frequently\u00a0in the temporal cortex and tended to be more common than\u00a0A\u03b240 plaques across species. Conversely, vascular A\u03b2 was labeled more consistently with A\u03b240 for each species on average. Although all individuals showed some degree of A\u03b240 and\/or A\u03b242 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 A\u03b240 vessel area and pretangle load in the hippocampus. This study demonstrates the co\u2010occurrence of A\u03b2 and tau pathology in two felid species, cheetahs and clouded leopards. Overall, these results provide an initial view of the manifestation of A\u03b2 and tau pathology in aged, large\u2010brained felids, which can be compared with markers of neurodegeneration across different taxa, including domestic cats, nonhuman primates, and humans.\n                  <\/jats:p>","DOI":"10.1002\/cne.25679","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:55:15Z","timestamp":1730282115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amyloid\u2010Beta, Tau, and Microglial Activation in Aged Felid Brains"],"prefix":"10.1002","volume":"532","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1607-8067","authenticated-orcid":false,"given":"Veronika","family":"Kulik","sequence":"first","affiliation":[{"name":"Department of Anthropology and Center for the Advanced Study of Human Paleobiology The George Washington University  Washington District of Columbia 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Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-449X","authenticated-orcid":false,"given":"Chet C.","family":"Sherwood","sequence":"additional","affiliation":[{"name":"Department of Anthropology and Center for the Advanced Study of Human Paleobiology The George Washington University  Washington District of Columbia 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