ArticleAnnals of neurology2024
FXTAS Neuropathology Includes Widespread Reactive Astrogliosis and White Matter Specific Astrocyte Degeneration.
Article in Annals of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 16 citations in OpenAlex.
- DNA Methylation and Proteomic Profiling of Postmortem Brain Tissue Reveals Epigenetic Dysregulation and Neuroinflammatory in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).bioRxiv : the preprint server for biology · 2026Article
- Distinctive hydrocephalus-like phenotype in NOTCH2NLC-related neuronal intranuclear inclusion disease: clinicopathological features and therapeutic implications.Acta neuropathologica communications · 2026Article
- The Tale of the Guanosine Tract in Repeat Expansion Disorders.Molecular neurobiology · 2026Review
- Article
- Use of the Behavioral Dyscontrol Scale-2 (BDS-2) to measure executive dysfunction in FXTAS.Frontiers in molecular neuroscience · 2026Article
- Glymphatic dysfunction and neuroinflammation in FXTAS: evidence from DTI-ALPS and gene expression analysis.Frontiers in molecular neuroscience · 2026Article
- Essential tremor-like phenotype in Fragile X carrier women.Clinical parkinsonism & related disorders · 2026Article
- Article
- Bringing fragile X-associated neuropsychiatric disorders into the phenotypic fold of premutation conditions.Brain : a journal of neurology · 2025Article
- Role of astrocytes in the pathogenesis of perinatal brain injury.Molecular medicine (Cambridge, Mass.) · 2025Review
- Polyglycine-mediated aggregation of FAM98B disrupts tRNA processing in GGC repeat disorders.Science (New York, N.Y.) · 2025Article
- Premutation Females with preFXTAS.International journal of molecular sciences · 2025Article
- Cell Sheets Formation Enhances Therapeutic Effects of Human Umbilical Cord Mesenchymal Stem Cells on Spinal Cord Injury.CNS neuroscience & therapeutics · 2024Article
- Review
- White matter astrocyte degeneration in FXTAS.Nature reviews. Neurology · 2024Article
- Comprehensive, multidisciplinary care for fragile X-associated tremor/ataxia syndrome.Frontiers in neurologyReview
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7 authors at 2 institutions in 1 country.
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Abstract
objectiveFragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset progressive genetic neurodegenerative disorder that occurs in FMR1 premutation carriers. The temporal, spatial, and cell-type specific patterns of neurodegeneration in the FXTAS brain remain incompletely characterized. Intranuclear inclusion bodies are the neuropathological hallmark of FXTAS, which are largest and occur most frequently in astrocytes, glial cells that maintain brain homeostasis. Here, we characterized neuropathological alterations in astrocytes in multiple regions of the FXTAS brain.
methodsStriatal and cerebellar sections from FXTAS cases (n = 12) and controls (n = 12) were stained for the astrocyte markers glial fibrillary acidic protein (GFAP) and aldehyde dehydrogenase 1L1 (ALDH1L1) using immunohistochemistry. Reactive astrogliosis severity, the prevalence of GFAP+ fragments, and astrocyte density were scored. Double label immunofluorescence was utilized to detect co-localization of GFAP and cleaved caspase-3.
resultsFXTAS cases showed widespread reactive gliosis in both grey and white matter. GFAP staining also revealed remarkably severe astrocyte pathology in FXTAS white matter - characterized by a significant and visible reduction in astrocyte density (-38.7% in striatum and - 32.2% in cerebellum) and the widespread presence of GFAP+ fragments reminiscent of apoptotic bodies. White matter specific reductions in astrocyte density were confirmed with ALDH1L1 staining. GFAP+ astrocytes and fragments in white matter were positive for cleaved caspase-3, suggesting that apoptosis-mediated degeneration is responsible for reduced astrocyte counts.
interpretationWe have established that FXTAS neuropathology includes robust degeneration of astrocytes, which is specific to white matter. Because astrocytes are essential for maintaining homeostasis within the central nervous system, a loss of astrocytes likely further exacerbates neuropathological progression of other cell types in the FXTAS brain. ANN NEUROL 2024;95:558-575.
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