Novel Blood Biomarkers Are Associated with White Matter Lesions in Fragile X- Associated Tremor/Ataxia Syndrome

Danuta Z. Loesch, Sarah J. Annesley, Nicholas Trost, Minh Q. Bui, Sui T. Lay, Elsdon Storey, Shawn W. De Piazza, Oana Sanislav, Lisa M. Francione, Eleanor M. Hammersley, Flora Tassone, David Francis, Paul R. Fisher

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background: The need for accessible cellular biomarkers of neurodegeneration in carriers of the fragile X mental retardation 1 (FMR1) premutation (PM) alleles. Objective: To assess the mitochondrial status and respiration in blood lymphoblasts from PM carriers manifesting the fragile X-associated tremor/ataxia syndrome (FXTAS) and non-FXTAS carriers, and their relationship with the brain white matter lesions. Methods: Oxygen consumption rates (OCR) and ATP synthesis using a Seahorse XFe24 Extracellular Flux Analyser, and steady-state parameters of mitochondrial function were assessed in cultured lymphoblasts from 16 PM males (including 11 FXTAS patients) and 9 matched controls. The regional white matter hyperintensity (WMH) scores were obtained from MRI. Results: Mitochondrial respiratory activity was significantly elevated in lymphoblasts from PM carriers compared with controls, with a 2- to 3-fold increase in basal and maximum OCR attributable to complex I activity, and ATP synthesis, accompanied by unaltered mitochondrial mass and membrane potential. The changes, which were more advanced in FXTAS patients, were significantly associated with the WMH scores in the supratentorial regions. Conclusion: The dramatic increase in mitochondrial activity in lymphoblasts from PM carriers may represent either the early stages of disease (specific alterations in short-lived blood cells) or an activation of the lymphocytes under pathological situations. These changes may provide early, convenient blood biomarkers of clinical involvements.

Original languageEnglish (US)
Pages (from-to)22-30
Number of pages9
JournalNeurodegenerative Diseases
StateAccepted/In press - Sep 8 2016


  • Blood lymphoblasts
  • Cellular biomarkers
  • Fragile X mental retardation 1 premutation
  • Fragile X-associated tremor/ataxia syndrome
  • Mitochondrial respiration
  • White matter hyperintensities

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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