Aim The present study aims at investigating the possible correlation between peripheral markers of inflammation and brain networks in amyotrophic lateral sclerosis (ALS) Introduction Among the complex mechanisms contributing to the pathogenesis of ALS neuroinflammation, which is associated with altered circulating cytokine levels, is suggested to play a prominent role. Methods Based on magnetoencephalography data, we estimated topological properties of the brain networks in ALS patients and healthy controls. Subsequently, the blood levels of a subset of cytokines were assayed. Finally, we modelled the brain topological features in function of the cytokines levels. Results Significant differences were found in the levels of the cytokines IL-4, IL-1β and IFN-γ between patients and controls. In particular, IL-4 and IL-1β levels increased in ALS patients, while the IFN-γ level was higher in healthy controls. We also detected modifications in brain global topological parameters in terms of hyper-connectedness. Despite both blood cytokines and brain topology were altered in ALS patients, such changes do not appear to be in a direct relationship. Conclusion Our results would be in line with the idea that topological changes relate to neurodegenerative processes. However, the absence of correlation between blood cytokines and topological parameters of brain networks does not preclude that inflammatory processes contribute to the alterations of the brain networks. Impact Statement The progression of ALS entails both neurodegenerative and inflammatory processes. Furthermore, disease progression induces global modifications of the brain networks, with advanced stages showing a more compact, hyper-connected network topology. In this paper, we hypothesized that the global inflammatory profile would relate to the topological alterations. Our results showed that this is not the case, as modelling the topological properties as a function of the inflammatory state did not yield good predictions. Hence, our results suggest that topological changes might directly relate to neurodegenerative processes instead.

In amyotrophic lateral sclerosis blood cytokines are altered, but do not correlate with changes in brain topology

Minino, Roberta;Pesoli, Matteo;Sorrentino, Giuseppe
;
Sorrentino, Pierpaolo
2020-01-01

Abstract

Aim The present study aims at investigating the possible correlation between peripheral markers of inflammation and brain networks in amyotrophic lateral sclerosis (ALS) Introduction Among the complex mechanisms contributing to the pathogenesis of ALS neuroinflammation, which is associated with altered circulating cytokine levels, is suggested to play a prominent role. Methods Based on magnetoencephalography data, we estimated topological properties of the brain networks in ALS patients and healthy controls. Subsequently, the blood levels of a subset of cytokines were assayed. Finally, we modelled the brain topological features in function of the cytokines levels. Results Significant differences were found in the levels of the cytokines IL-4, IL-1β and IFN-γ between patients and controls. In particular, IL-4 and IL-1β levels increased in ALS patients, while the IFN-γ level was higher in healthy controls. We also detected modifications in brain global topological parameters in terms of hyper-connectedness. Despite both blood cytokines and brain topology were altered in ALS patients, such changes do not appear to be in a direct relationship. Conclusion Our results would be in line with the idea that topological changes relate to neurodegenerative processes. However, the absence of correlation between blood cytokines and topological parameters of brain networks does not preclude that inflammatory processes contribute to the alterations of the brain networks. Impact Statement The progression of ALS entails both neurodegenerative and inflammatory processes. Furthermore, disease progression induces global modifications of the brain networks, with advanced stages showing a more compact, hyper-connected network topology. In this paper, we hypothesized that the global inflammatory profile would relate to the topological alterations. Our results showed that this is not the case, as modelling the topological properties as a function of the inflammatory state did not yield good predictions. Hence, our results suggest that topological changes might directly relate to neurodegenerative processes instead.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11367/86611
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