Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan;37(1):218-224.
doi: 10.1002/mds.28825. Epub 2021 Oct 13.

Neuroinflammation in the Cerebellum and Brainstem in Friedreich Ataxia: An [18F]-FEMPA PET Study

Wasim Khan  1 , Louise A Corben  2   3   4 , Hiba Bilal  4 , Lucy Vivash  1 , Martin B Delatycki  2   3   5 , Gary F Egan  4   6 , Ian H Harding  1   6
Affiliations

Neuroinflammation in the Cerebellum and Brainstem in Friedreich Ataxia: An [18F]-FEMPA PET Study

Wasim Khan et al. Mov Disord. 2022 Jan.

Abstract

Background: Neuroinflammation is proposed to accompany, or even contribute to, neuropathology in Friedreich ataxia (FRDA), with implications for disease treatment and tracking.

Objectives: To examine brain glial activation and systemic immune dysfunction in people with FRDA and quantify their relationship with symptom severity, duration, and onset age.

Methods: Fifteen individuals with FRDA and 13 healthy controls underwent brain positron emission tomography using the translocator protein (TSPO) radioligand [18 F]-FEMPA, a marker of glial activation, together with the quantification of blood plasma inflammatory cytokines.

Results: [18 F]-FEMPA binding was significantly increased in the dentate nuclei (d = 0.67), superior cerebellar peduncles (d = 0.74), and midbrain (d = 0.87), alongside increased plasma interleukin-6 (IL-6) (d = 0.73), in individuals with FRDA compared to controls. Increased [18 F]-FEMPA binding in the dentate nuclei, brainstem, and cerebellar anterior lobe correlated with earlier age of symptom onset (controlling for the genetic triplet repeat expansion length; all r part < -0.6), and in the pons and anterior lobe with shorter disease duration (r = -0.66; -0.73).

Conclusions: Neuroinflammation is evident in brain regions implicated in FRDA neuropathology. Increased neuroimmune activity may be related to earlier disease onset and attenuate over the course of the illness. © 2021 International Parkinson and Movement Disorder Society.

Keywords: TSPO; brain; inflammation; microglia; spinocerebellar.

PubMed Disclaimer

References

    1. Delatycki MB, Corben LA. Clinical features of Friedreich ataxia. J Child Neurol 2012;27(9):1133-1137.
    1. Koeppen AH, Mazurkiewicz JE. Friedreich ataxia: neuropathology revised. J Neuropathol Exp Neurol 2013;72(2):78-90.
    1. Harding IH, Lynch DR, Koeppen AH, Pandolfo M. Central nervous system therapeutic targets in Friedreich ataxia. Hum Gene Ther 2020;31(23-24):1226-1236.
    1. Selvadurai LP, Harding IH, Corben LA, Georgiou-Karistianis N. Cerebral abnormalities in Friedreich ataxia: a review. Neurosci Biobehav Rev 2018;84:394-406.
    1. Jasoliya MJ, McMackin MZ, Henderson CK, Perlman SL, Cortopassi GA. Frataxin deficiency impairs mitochondrial biogenesis in cells, mice and humans. Hum Mol Genet 2017;26(14):2627-2633.

Publication types

MeSH terms

LinkOut - more resources