Domestic cats (Felis catus) are known to develop cognitive impairment, and several small series have demonstrated both β-amyloid and tau aggregation, including neurofibrillary tangles, with age, making them a promising physiologic model of Alzheimer disease (AD). We therefore report the largest feline autopsy cohort to date of 32 cats ranging from 1.5 to 22.1 years of age, with systematic neuropathologic assessment according to NIA-Alzheimer's Association Criteria. Formalin-fixed paraffin-embedded tissue sections of brain were obtained retrospectively from cats autopsied at the Iowa State College of Veterinary Medicine. We found β-amyloid staining, predominantly in Cortical Layers IV and VI in 27 of the 32 cats used in the study, with four of these animals showing tau-positive tangles and neuropil threads. In 75% of these cases (3/4), tau deposition was limited to entorhinal cortex, while one case showed diffuse positive staining throughout the hippocampal formation and neocortex. This last case showed positive staining for all phospho-tau-specific antibodies tested, similar to the pattern seen in human AD. Interestingly, we saw a higher ratio of pretangles to tangles than that in human AD, and none of the cases showed neuritic plaques on any of the stains used. Our findings indicate that aging domestic cats spontaneously develop both β-amyloid and tau pathology similar, but not identical to that seen in human AD. This suggests that the domestic cat may serve as a potential model for mechanistic and therapeutic AD studies, but that additional research is needed to identify differences between the neuropathology of aging in humans and felines.
Keywords: AT8 (RRID: AB_223647); Alzheimer disease; CP13 (RRID: AB_2314223); PHF1 (RRID: AB_2315150); RZ3 (RRID: AB_2716721); S214 (RRID: AB_1502105); THR205 (RRID: AB_2533738); Uniprot (RRID: SCR_002380); animal models; cats; neurodegeneration; neuropathology; tau protein; β-amyloid; β-amyloid (RRID: AB_2564652).
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