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

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 [F-18]-FEMPA, a marker of glial activation, together with the quantification of blood plasma inflammatory cytokines. Results [F-18]-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 [F-18]-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. (c) 2021 International Parkinson and Movement Disorder Society

Automated summary

Neuroinflammation is significantly increased in certain brain regions of individuals with FRDA, and is related to the severity, duration, and age of onset of the disease. These findings suggest that neuroimmune activity may play a role in the pathogenesis and progression of FRDA.