Objective: To investigate the relationship between CSF α-synuclein levels and EEG-based network properties, aiming to clarify their role in PD pathophysiology.

Background: Parkinson’s disease (PD) is characterized by the pathological aggregation of α-synuclein, which spreads through the brain in a prion-like manner [1]. PD patients present band-specific functional connectivity (FC) alterations since the early stage [2]. Intrinsic graph properties are also critical for network efficiency. Among these, the scale-free organization, characterized by a few highly connected hubs and many sparsely connected nodes, is crucial in maintaining network robustness and optimizing communication [3].

Method: 40 early-stage PD patients and 40 healthy controls (HC) were included in the study. CSF α-synuclein levels were assessed in PD. 64-channel EEG recordings were used to compute FC across θ-α-β-low-γ bands. The sigma coefficient (σ), which describes the degree distribution following a power law, was used to assess the scale-free network topology [4]. Moreover, hub regions were identified using betweenness centrality.

Results: PD patients showed a higher σ coefficient than HC (p<0.001) in β-band, indicating a more scale-free organization. No significant differences were found in the other bands. Moreover, we observed a negative correlation (r=-0.61 p=0.002) between σ coefficientand CSF α-synuclein levels in our PD cohort in the β-band. The analysis also revealed a significant negative correlation between CSF α-synuclein levels and β-band betweenness centrality in specific regions, particularly in parahippocampal and entorhinal cortex.

Conclusion: These findings indicated that α-synuclein accumulation in PD may be influenced by β-band cortical network properties. Brain β networks characterized by a few highly connected hub nodes and many secondary, sparsely connected nodes could lead to greater accumulation of α-synuclein in the brain [5].  The parahippocampal and entorhinal cortices, regions affected early in PD, may act as critical hubs facilitating the propagation of α-synuclein, highlighting the importance of network topology in disease progression. Although preliminary, our results suggest that future therapies selectively modulating the β-band network could represent a novel approach to slowing α-synuclein propagation and PD progression.

References: [1] H. Braak, E. Ghebremedhin, U. Rüb, H. Bratzke, and K. Del Tredici, “Stages in the development of Parkinson’s disease-related pathology,” Cell Tissue Res, vol. 318, no. 1, pp. 121–134, 2004, doi: 10.1007/s00441-004-0956-9.
[2] M. Conti et al., “Band-Specific Altered Cortical Connectivity in Early Parkinson’s Disease and its Clinical Correlates,” Movement Disorders, pp. 1–13, 2023, doi: 10.1002/mds.29615.
[3] L. Pini, S. Lista, A. Griffa, G. Allali, and B. P. Imbimbo, “Can brain network connectivity facilitate the clinical development of disease-modifying anti-Alzheimer drugs?,” Brain Commun, vol. 7, no. 1, Dec. 2024, doi: 10.1093/braincomms/fcae460.
[4] P. Ciuciu, P. Abry, and B. J. He, “Interplay between functional connectivity and scale-free dynamics in intrinsic fMRI networks,” Neuroimage, vol. 95, 2014, doi: 10.1016/j.neuroimage.2014.03.047.
[5] B. Mollenhauer et al., “Longitudinal analyses of cerebrospinal fluid α-Synuclein in prodromal and early Parkinson’s disease,” Movement Disorders, vol. 34, no. 9, 2019, doi: 10.1002/mds.27806.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/contribution-of-%ce%b2-band-functional-connectivity-to-the-%ce%b1-synuclein-propagation-in-early-stage-parkinsons-disease-insights-from-the-analysis-of-brain-network-properties/