Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriers

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16 Scopus citations


Premutation carriers have a 55-200 CGG expansion in the fragile X mental retardation 1 (FMR1) gene. Currently, 1.5 million individuals are affected in the United States, and carriers are at risk of developing the late-onset neurodegenerative disorder Fragile X-associated tremor ataxia syndrome (FXTAS). Limited efforts have been made to develop new methods for improved early patient monitoring, treatment response, and disease progression. To this end, plasma metabolomic phenotyping was obtained for 23 premutation carriers and 16 age- and sex-matched controls. Three biomarkers, phenylethylamine normalized by either aconitate or isocitrate and oleamide normalized by isocitrate, exhibited excellent model performance. The lower phenylethylamine and oleamide plasma levels in carriers may indicate, respectively, incipient nigrostriatal degeneration and higher incidence of substance abuse, anxiety and sleep disturbances. Higher levels of citrate, isocitrate, aconitate, and lactate may reflect deficits in both bioenergetics and neurotransmitter metabolism (Glu, GABA). This study lays important groundwork by defining the potential utility of plasma metabolic profiling to monitor brain pathophysiology in carriers before and during the progression of FXTAS, treatment efficacy and evaluation of side effects.

Original languageEnglish (US)
Article number71
JournalFrontiers in Molecular Neuroscience
Issue numberAUG
StatePublished - Aug 12 2016


  • Fragile X
  • Metabolomics
  • Mitochondrial dysfunction
  • Neurodegeneration
  • Trinucleotide repeat disease

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology


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