Objective: The purpose of this study is to examine the distribution of tau pathology in brain regions of patients with spinocerebellar ataxia type 8 (SCA8).

Background: SCA8 is a neurodegenerative condition that presents with several neurological symptoms such as cerebellar ataxia, parkinsonism, pyramidal signs, and cognitive impairment. SCA8 is caused by a CTA/CTG repeat expansion located on chromosome 13q21 (ataxin 8 opposite strand: ATXN8OS). Abnormal CTA/CTG repeat expansion in ATXN8OS is also found in other neurodegenerative diseases such as progressive supranuclear palsy and Parkinson’s disease.

Method: Neuropathological examination of two patients with genetically confirmed SCA8 was performed. Immunohistochemistry for p-tau, 3-repeat tau (3R-tau), and 4-repeat tau (4R-tau) was used to assess tau pathology. Patient #1 was a Japanese man who developed gait disturbance at age 58, showed cerebellar atrophy on brain magnetic resonance imaging, and died of respiratory failure at age 84. Patient #2 was a Japanese man who developed gait disturbance at age 43, began to show progressive dysphagia and dysarthria from age 67, and died of acute pancreatitis at age 76.

Results: Prominent loss of Purkinje cells, atrophy of the molecular layer, and proliferation of Bergmann glia were observed in the cerebellum of both patients. Neuronal loss in the substantia nigra was also observed in both patients. In patient #1, neurofibrillary tangles (NFTs) as well as glial inclusions immunopositive for p-tau and 4R-tau were visible in the inferior olivary nuclei, pontine nuclei, substantia nigra, dentate nucleus, subthalamic nucleus, pallidum, putamen, and motor cortex. In patient #2, globose-type NFTs and glial inclusions were visible in several brain regions including the striatum, substantia nigra, oculomotor nucleus, locus coeruleus, pontine nuclei, and reticular formation in the medulla oblongata, which were positive for 3R- and/or 4R-tau.

Conclusion: Neurodegeneration, predominantly in the substantia nigra, and accumulation of abnormal tau proteins were found in both patients with SCA8. The present study suggests a relationship between abnormal CTA/CTG repeat expansion in ATXN8OS and tauopathy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuropathological-profile-of-tauopathy-in-spinocerebellar-ataxia-type-8/