SCA1 is an autosomal-dominant disease characterized by progressive cerebellar ataxia. It accounts for ~6% of cerebellar ataxias worldwide. SCA1 presents gradual loss of balance and coordination, compromised cognition, gaze palsy, peripheral neuropathy, and motor control symptoms features common for spinocerebellar ataxias. The predominant pathological attributes are atrophy, gliosis, and severe loss of Purkinje cells in the cerebellum. Patients experience coordination difficulties, including dysarthria, dysphagia, and ophthalmoplegia. SCA1 is caused by a CAG repeat expansion in the coding region of the ataxin-1 (ATXN1) gene. This repeat is highly polymorphic, with 6-44 triplets in healthy individuals. Increased phosphorylation of polyQ-expanded ataxin-1 contributes to SCA1 pathology, so inhibition of these kinases may provide a therapeutic target. 97 SCA2 is also an autosomal-dominant, progressive ataxia that accounts for ~13% of cerebellar ataxia cases. The main characteristic clinical feature of SCA2 is exceedingly slow saccade eye movements. Other symptoms include difficulties with coordinated movement and action tremor (uncommon with the other ataxias), myoclonus, and reduction in appetite. Occasionally, SCA2 patients present with parkinsonian characteristics, or have extensive motor neuron disease. SCA2 patients typically exhibit atrophy of the cerebellum and brainstem, with severe degeneration of cerebellar Purkinje cells and granule cells combined with neuron loss and gliosis. Degeneration of the substantia nigra, producing parkinsonism, and/or atrophy of the frontotemporal lobes may occur sometimes. 100, 101 SCA2 is caused by a CAG repeat expansion in the ataxin-2 (ATXN2) gene. Unlike the other polyQ diseases, SCA2 patients exhibit mainly cytoplasmic, rather than nuclear, inclusions. 103 SCA3, a.k.a. Machado-Joseph disease, is the most common autosomal-dominant cerebellar ataxia worldwide. SCA3 typically show symptoms in young adults or in middle age with slowly progressive and highly variable syndromes attributed to four clinical subtypes. Each of them has a core presentation of cerebellar ataxia, dysphagia, dystonia, pyramidal signs, progressive external ophthalmoplegia, and muscle atrophy, as well as weight loss and restlesslegs syndrome. 104, 105 SCA3 is unique among other SCAs with neuron loss being often mild in Purkinje cells of the cerebellum. 106, 107 SCA3 is caused by a CAG repeat expansion near the 3' end of the coding region of the ataxin-3 (ATXN3) gene. Alleles in healthy individuals range from 12 to 40 CAG repeats, while diseased ones carry 55-84 CAG repeats. SCA6 is an autosomal-dominant, slowly progressive cerebellar ataxia. The average age of onset is in the 5 th decade of life, with most patients presenting gait/upper-limb incoordination, intention tremor, dysarthria, dysphagia, and diplopia. Vertical nystagmus, horizontal gazeevoked nystagmus, and difficulty fixating on moving objects are common clinical features. Neuropathology examination shows distinct cerebellar atrophy with severe loss of Purkinje cells and moderate loss of cerebellar granule cells. SCA6 is caused by a CAG repeat expansion in exon 47 of the CACNA1A gene. Pathogenic alleles range from 19 to 33 CAG repeats, while healthy individuals possess alleles with 4-18 CAG repeats. CAG repeat size differences are small in comparison to other polyQ repeat diseases, and somatic instability is minimal. 114 SCA7 is an autosomal-dominant, rapidly progressive cerebellar ataxia associated with visual impairment. SCA7 shows a wide geographic distribution, and a prevalence of ~1/500,000. Patients display pronounced dysarthria and can develop visual impairment due to a cone-rod dystrophy form of retinal degeneration, ultimately leading to blindness. Neurodegeneration and reactive gliosis occur in the cerebellar cortex, dentate nucleus, inferior olive, pontine nuclei, and occasionally the basal ganglia. Cerebellar tissue from SCA7 patients exhibits extensive loss of cerebellar Purkinje cells. As with other polyQ diseases, nuclear inclusions are common in vulnerable populations. SCA7 is caused by a CAG repeat expansion at the 5' end of the coding region of the ataxin-7 gene. While healthy individuals possess alleles ranging in size from 7 to 35 CAGs, diseased expanded SCA7 CAG repeats are among the most unstable of all coding repeat expansions, with patients having 37 to >300 repeats. 124 SCA17 is an extremely rare dominantly inherited cerebellar ataxia, with <100 families reported. Ataxia and psychiatric abnormalities are common at the beginning, later accompanied by chorea and dystonia, dementia, pyramidal signs, rigidity, and, rarely, parkinsonism. Neuropathology involves atrophy of the cortex, striatum, and cerebellum, with neuron loss in the striatum and cerebellar Purkinje cell layer. 127 SCA17 is caused by a CAG repeat expansion in the TATA-binding protein gene on chromosome 6q27. Normal alleles contain 25-48 CAG repeats, while those in diseased individuals contain 43-66 CAG repeats. Age of onset is variable, from early childhood to middle age, and SCA17 ancestries exhibit anticipation. Patients also display nuclear inclusions. (Another spinocerebellar ataxia, SCA12, is also caused by a CAG repeat expansion, however it is not transcribed to polyglutaminethe repeat expansion is located in a non-coding region of a gene, so it is not considered a polyQ (polyglutamine) disease. )