Brain atrophy and white matter damage linked to peripheral bioenergetic deficits in the neurodegenerative disease fxtas

Junyi Wang, Eleonora Napoli, Kyoungmi Kim, Yingratana A. McLennan, Randi J. Hagerman, Cecilia Giulivi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting subjects (premutation carriers) with a 55-200 CGG-trinucleotide expansion in the 5UTR of the fragile X mental retardation 1 gene (FMR1) typically after age 50. As both the presence of white matter hyperintensities (WMHs) and atrophied gray matter on magnetic resonance imaging (MRI) are linked to age-dependent decline in cognition, here we tested whether MRI outcomes (WMH volume (WMHV) and brain volume) were correlated with mitochondrial bioenergetics from peripheral blood monocytic cells in 87 carriers with and without FXTAS. As a parameter assessing cumulative damage, WMHV was correlated to both FXTAS stages and age, and brain volume discriminated between carriers and non-carriers. Similarly, mitochondrial mass and ATP production showed an age-dependent decline across all participants, but in contrast to WMHV, only FADH2-linked ATP production was significantly reduced in carriers vs. non-carriers. In carriers, WMHV negatively correlated with ATP production sustained by glucose-glutamine and FADH2-linked substrates, whereas brain volume was positively associated with the latter and mitochondrial mass. The observed correlations between peripheral mitochondrial bioenergetics and MRI findings—and the lack of correlations with FXTAS diagnosis/stages—may stem from early brain bioenergetic deficits even before overt FXTAS symptoms and/or imaging findings.

Original languageEnglish (US)
Article number9171
JournalInternational journal of molecular sciences
Issue number17
StatePublished - Sep 1 2021


  • Aging
  • Bioenergetics
  • Brain
  • Cognition
  • FMR1
  • Mitochondria
  • MRI
  • Peripheral blood monocytic cells
  • Volume
  • White matter hyperintensities

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


Dive into the research topics of 'Brain atrophy and white matter damage linked to peripheral bioenergetic deficits in the neurodegenerative disease fxtas'. Together they form a unique fingerprint.

Cite this