Primary Feline Tauopathy: Clinical, Morphological, Immunohistochemical, and Genetic Studies

Abstract

Simple Summary Tauopathies are a group of neurodegenerative diseases where a specific protein called tau accumulates and forms aggregates in neurons and glial cells. In humans, these diseases can be caused by only this protein (primary) or in combination with another one (secondary). Primary tauopathies are common in humans but rare in animals. We analyzed the development of tau pathology in 16 cats of different ages. A female cat showed progressive mental status and gait abnormalities over a six-year period. Brain imaging revealed a progressive shrinkage of the brain (atrophy). Due to a poor prognosis, the cat was euthanized at the age of ten years. Evaluation of the brain tissue showed significant loss of neurons in the parietal cortex and Purkinje cells in the cerebellum. Immunohistochemistry identified abnormal tau protein aggregates in neurons (referred to as pre-tangles) and oligodendrocytes (referred to as coiled bodies). Genetic testing did not reveal any known genetic alteration associated with this disease. None of the other 15 cats studied showed similar clinical signs or brain changes. This is the first reported case of primary tauopathy in an adult cat that presented the first neurological signs when she was four years old.Abstract Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of hyperphosphorylated tau in neurons and glia. Primary tauopathies are not uncommon in humans but exceptional in other species. We evaluate the clinical, neuropathological, and genetic alterations related to tau pathology in 16 cats aged from 1 to 21 years with different clinical backgrounds. Interestingly, a 10-year-old female cat presented a six-year progressive history of mental status and gait abnormalities. The imaging study revealed generalized cortical atrophy. Due to the poor prognosis, the cat was euthanatized at the age of ten. Neuropathological lesions were characterized by massive neuronal loss with marked spongiosis and associated moderate reactive gliosis in the parietal cortex, being less severe in other areas of the cerebral cortex, and the loss of Purkinje cells of the cerebellum. Immunohistochemical methods revealed a 4R-tauopathy with granular pre-tangles in neurons and coiled bodies in oligodendrocytes. Deposits were recognized with several phospho-site antibodies (4Rtau, tau5, AT8, PFH, tau-P Thr181, tau-P-Ser 262, tau-P Ser 422) and associated with increased granular expression of active tau kinases (p38-P Thr180/Tyr182 and SAPK/JNK-P Thr138/Thr185). The genetic study revealed well-preserved coding regions of MAPT. No similar alterations related to tau pathology were found in the other 15 cats processed in parallel. To our knowledge, this is the first case reporting a primary 4R-tauopathy with severe cerebral and Purkinje cell degeneration in an adult cat with neurological signs starting at a young age.