Cerebral Microbleeds in Fragile X–Associated Tremor/Ataxia Syndrome

María Jimena Salcedo-Arellano, Jun Yi Wang, Yingratana A. McLennan, Mai Doan, Ana Maria Cabal-Herrera, Sara Jimenez, Marisol W. Wolf-Ochoa, Desiree Sanchez, Pablo Juarez, Flora Tassone, Blythe Durbin-Johnson, Randi J. Hagerman, Verónica Martínez-Cerdeño

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Fragile X–associated tremor/ataxia syndrome is a neurodegenerative disease of late onset developed by carriers of the premutation in the fragile x mental retardation 1 (FMR1) gene. Pathological features of neurodegeneration in fragile X–associated tremor/ataxia syndrome include toxic levels of FMR1 mRNA, ubiquitin-positive intranuclear inclusions, white matter disease, iron accumulation, and a proinflammatory state. Objective: The objective of this study was to analyze the presence of cerebral microbleeds in the brains of patients with fragile X–associated tremor/ataxia syndrome and investigate plausible causes for cerebral microbleeds in fragile X–associated tremor/ataxia syndrome. Methods: We collected cerebral and cerebellar tissue from 15 fragile X–associated tremor/ataxia syndrome cases and 15 control cases carrying FMR1 normal alleles. We performed hematoxylin and eosin, Perls and Congo red stains, ubiquitin, and amyloid β protein immunostaining. We quantified the number of cerebral microbleeds, amount of iron, presence of amyloid β within the capillaries, and number of endothelial cells containing intranuclear inclusions. We evaluated the relationships between pathological findings using correlation analysis. Results: We found intranuclear inclusions in the endothelial cells of capillaries and an increased number of cerebral microbleeds in the brains of those with fragile X–associated tremor/ataxia syndrome, both of which are indicators of cerebrovascular dysfunction. We also found a suggestive association between the amount of capillaries that contain amyloid β in the cerebral cortex and the rate of disease progression. Conclusion: We propose microangiopathy as a pathologic feature of fragile X–associated tremor/ataxia syndrome.

Original languageEnglish (US)
JournalMovement Disorders
StateAccepted/In press - 2021


  • cerebral microbleeds
  • FMR1 premutation
  • neurodegeneration

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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