A Majority of FXTAS Cases Present with Intranuclear Inclusions Within Purkinje Cells
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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder that affects carriers of a FMR1 premutation. Symptoms include cerebellar ataxia, tremor, and cognitive deficits. The most characteristic pathology of FXTAS is the presence of eosinophilic ubiquitin-positive intranuclear inclusions in neurons and astrocytes throughout the nervous system and non-nervous tissues. Inclusions are present in neurons throughout the brain but are widely believed not to be present in the Purkinje cells (PCs) of the cerebellum. However, we analyzed 26 postmortem cases of FXTAS and demonstrated that 65 % of cases presented with inclusions within PCs of the cerebellum. We determined that the presence or absence of inclusions in PCs is correlated with age and that those cases with PC inclusions were overall 11 years older than those with no PC inclusions. Half of the cases with PCs with inclusions presented with twin nuclear inclusions. This novel finding demonstrating the presence of inclusions within PCs provides an insight into the understanding of the FXTAS motor symptoms and provides a novel target for the development of therapeutic strategies.
KeywordsFXTAS FRMP Ubiquitin Purkinje cells Cerebellum
This work was supported by the National Institute of Health grants MH094681 (Dr. Martínez-Cerdeño), HD040661 (Dr. P Hagerman), HD036071 (covered brain collection), and by the Department of Pathology and Laboratory Medicine at UC Davis and the Shriners Hospitals.
Compliance with Ethical Standards
All tissue samples were obtained through consented autopsies with institutional review board approval.
Conflict of Interest
The authors declare that they have no conflict of interest.
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