TY - JOUR
T1 - Cerebral Microbleeds in Fragile X–Associated Tremor/Ataxia Syndrome
AU - Salcedo-Arellano, María Jimena
AU - Wang, Jun Yi
AU - McLennan, Yingratana A.
AU - Doan, Mai
AU - Cabal-Herrera, Ana Maria
AU - Jimenez, Sara
AU - Wolf-Ochoa, Marisol W.
AU - Sanchez, Desiree
AU - Juarez, Pablo
AU - Tassone, Flora
AU - Durbin-Johnson, Blythe
AU - Hagerman, Randi J.
AU - Martínez-Cerdeño, Verónica
N1 - Publisher Copyright:
© 2021 International Parkinson and Movement Disorder Society
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - cerebral microbleeds
KW - FMR1 premutation
KW - FXTAS
KW - neurodegeneration
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U2 - 10.1002/mds.28559
DO - 10.1002/mds.28559
M3 - Article
C2 - 33760253
AN - SCOPUS:85102940670
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
ER -