Neuropathology of spinocerebellar ataxia type 8: Common features and unique tauopathy

Yonenobu, Yuki; Beck, Goichi; Kido, Kansuke; Maeda, Norihisa; Yamashita, Ryo; Inoue, Koichiro; Saito, Yuko; Hasegawa, Masato; Ito, Hidefumi; Hasegawa, Kazuko; Morii, Eiichi; Iwaki, Toru; Murayama, Shigeo; Mochizuki, Hideki

doi:10.1111/neup.12894

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…It has been confirmed that tauopathy was present in 2 cases of SCA8 autopsy, one of which exhibited 4-repeat tauopathy resembling PSP. 9 This finding reveals the complexity of SCA8 as a repeat expansion disease and highlights the necessity for further pathological research to elucidate the relationship between SCA8 and tauopathy.…”

Section: Discussionmentioning

confidence: 82%

Spinocerebellar ataxia type 8 presents as progressive supranuclear palsy

Jiang

Zhu

Zhao

et al. 2023

NSJ

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Spinocerebellar ataxia type 8 is a progressive neurodegenerative disease induced by expansion of CTA/CTG repeats in an untranslated region of the ATXN8/ATXN8OS gene. We report an elderly female patient presenting with rigidity, bradykinesia, ataxia and oculomotor defect at the disease onset age of 65 years old without family history, and hummingbird sign in cranial MRI, initially diagnosed as progressive supranuclear palsy (PSP). But genetic test showed that one allele of ATXN8OS gene had more than 131 CTA/CTG repeats which was a full penetrance mutant. It’s possible that this is a case of PSP with an ATXN8OS gene mutation that doesn’t contribute to the phenotype. Whether the ATXN8OS gene CTA/CTG repeats cause PSP phenotype needs further investigation with larger samples and pathological findings.

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Section: Discussionmentioning

confidence: 82%

Spinocerebellar ataxia type 8 presents as progressive supranuclear palsy

Jiang

Zhu

Zhao

et al. 2023

NSJ

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“…The neuropathology of SCA8 is unclear now, and the studies have revealed several shared characteristics in the affected individuals, including pronounced neuronal loss in the substantia nigra, loss of Purkinje neurons, atrophy of the molecular layer, and heightened proliferation of radial glia in the cerebellum (Yonenobu et al, 2023 ). Furthermore, polyglutamine monoclonal antibody 1C2-positive intranuclear inclusions and pan-nuclear staining were observed in the Purkinje, medulla, and dentate nucleus of the human SCA8 brain.…”

Section: Discussionmentioning

confidence: 99%

Spastic paraplegia is the main manifestation of a spinocerebellar ataxia type 8 lineage in China: a case report and review of literature

Chen

Liu

et al. 2023

Front. Hum. Neurosci.

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The diagnosis and treatment of cerebellar atrophy remain challenging owing to its nonspecific symptoms and laboratory indicators. Three patients with spinocerebellar ataxia type 8 caused by ATXN8OS were found among the 16 people in the studied family. The clinical manifestations of the patients included progressive spastic paraplegia of the lower extremities, mild ataxia, mild cognitive impairment, and cerebellar atrophy. After administering antispasmodic rehabilitation treatment, using oral drugs, botulinum toxin injection, baclofen pump, and other systems in our hospital, the patients' lower extremity spasticity was significantly relieved. To our knowledge, till date, this is the first domestic report of spinocerebellar ataxia type 8 affecting a family, caused by ATXN8OS with spasticity onset in early childhood. Manifestations of the disease included spastic dyskinesia (in early disease stages) and cerebellar atrophy. Through systematic rehabilitation, the daily life of patients with this movement disorder was improved. This case report adds to the literature on spinocerebellar ataxia type 8 by summarizing its features.

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“…This condition, caused by pathogenic sequence variants in C19orf12 , was reported as a secondary tauopathy, as TAU pathology was reported by several studies [ 253 – 255 ]. Recently, TAU pathology was observed in some cases of spinocerebellar ataxia type 8 (SCA8), a condition caused by abnormal CTA/CTG repeat expansions in ATXN8OS which have also been reported in PSP [ 256 ]. However, a precise pathomechanistic connection to TAU has not yet been established in these cases.…”

Section: Secondary Tauopathiesmentioning

confidence: 99%

Genetic forms of tauopathies: inherited causes and implications of Alzheimer’s disease-like TAU pathology in primary and secondary tauopathies

Langerscheidt,

Wied,

Al Kabbani

et al. 2024

J Neurol

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Tauopathies are a heterogeneous group of neurologic diseases characterized by pathological axodendritic distribution, ectopic expression, and/or phosphorylation and aggregation of the microtubule-associated protein TAU, encoded by the gene MAPT. Neuronal dysfunction, dementia, and neurodegeneration are common features of these often detrimental diseases. A neurodegenerative disease is considered a primary tauopathy when MAPT mutations/haplotypes are its primary cause and/or TAU is the main pathological feature. In case TAU pathology is observed but superimposed by another pathological hallmark, the condition is classified as a secondary tauopathy. In some tauopathies (e.g. MAPT-associated frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Alzheimer's disease (AD)) TAU is recognized as a significant pathogenic driver of the disease. In many secondary tauopathies, including Parkinson's disease (PD) and Huntington's disease (HD), TAU is suggested to contribute to the development of dementia, but in others (e.g. Niemann-Pick disease (NPC)) TAU may only be a bystander. The genetic and pathological mechanisms underlying TAU pathology are often not fully understood. In this review, the genetic predispositions and variants associated with both primary and secondary tauopathies are examined in detail, assessing evidence for the role of TAU in these conditions. We highlight less common genetic forms of tauopathies to increase awareness for these disorders and the involvement of TAU in their pathology. This approach not only contributes to a deeper understanding of these conditions but may also lay the groundwork for potential TAU-based therapeutic interventions for various tauopathies.

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Neuropathology of spinocerebellar ataxia type 8: Common features and unique tauopathy

Cited by 4 publications

References 19 publications

Spinocerebellar ataxia type 8 presents as progressive supranuclear palsy

Spinocerebellar ataxia type 8 presents as progressive supranuclear palsy

Spastic paraplegia is the main manifestation of a spinocerebellar ataxia type 8 lineage in China: a case report and review of literature

Genetic forms of tauopathies: inherited causes and implications of Alzheimer’s disease-like TAU pathology in primary and secondary tauopathies

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