The Cerebellum

, Volume 15, Issue 5, pp 546–551 | Cite as

A Majority of FXTAS Cases Present with Intranuclear Inclusions Within Purkinje Cells

  • Jeanelle Ariza
  • Hailee Rogers
  • Angela Monterrubio
  • Adriana Reyes-Miranda
  • Paul J. Hagerman
  • Verónica Martínez-CerdeñoEmail author
Original Paper


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.


FXTAS 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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Jeanelle Ariza
    • 1
  • Hailee Rogers
    • 1
  • Angela Monterrubio
    • 1
  • Adriana Reyes-Miranda
    • 1
  • Paul J. Hagerman
    • 2
    • 3
  • Verónica Martínez-Cerdeño
    • 1
    • 2
    Email author
  1. 1.Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern CaliforniaUC Davis School of MedicineSacramentoUSA
  2. 2.MIND InstituteUC Davis Medical CenterSacramentoUSA
  3. 3.Department of Biochemistry and Molecular MedicineUC Davis School of MedicineSacramentoUSA

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