Scientific Paper News Report: Pathological Basis and Topological Properties of Structural Brain Networks in Parkinson’s Disease Patients

Background and Research Objectives

In Parkinson’s disease (PD), α-synuclein spreads between connected brain regions, leading to neuronal loss and brain network disruption. Using diffusion-weighted imaging (DWI), traditional measures of brain network organization and more advanced measures of brain network resilience can be captured. The purpose of this study is to explore which neuropathological processes lead to regional network topological changes and alterations in brain network resilience in PD patients.

Source of Research

This paper was written by scholars including Irene Frigerio, Tommy A.A. Broeders, Chen-Pei Lin, Maud M.A. Bouwman, Ismail Koubiyr, Frederik Barkhof, Henk W. Berendse, Wilma D.J. van de Berg, Linda Douw, and Laura E. Jonkman. The institutions involved are the Amsterdam University Medical Centers and University College London. The study was published in “Neurology®” in 2024, issue 103:e209678, DOI:10.1212/wnl.0000000000209678.

Research Methods

Subject Selection

In collaboration with the Netherlands Brain Bank (NBB) and Amsterdam Normal Aging Brain Collection (NABCA), we selected 34 brain donors, including 19 PD brain donors and 15 non-neurological disease control donors.

Brain Tissue Collection and MRI Scanning

Postmortem, 3D T1-weighted MRI and DWI scans were performed on whole-head specimens, followed by brain tissue collection. The scanning was done using a 3T MRI scanner (Signa MR750). Imaging data were preprocessed, and probabilistic tractography was used to generate brain structural connectivity matrices. Subsequently, regional eigenvector centrality and clustering coefficient, as well as brain network resilience (global efficiency changes after node failure), were calculated.

Tissue Processing and Immunohistochemistry

Post-dissection, brain tissues from eight cortical regions underwent immunohistochemical processing, marking pSer129 α-synuclein, phosphorylated tau protein, β-amyloid, neurofilament light chain (NFL), and synaptophysin. The pathological burden and degeneration of axons and synapses in each region were quantified.

Data Analysis

Statistical analysis was performed using R-studio 4.2.1, employing non-parametric rank-based tests and FDR (false discovery rate) correction to assess group differences and correlations.

Major Research Results

Regional Network Topological Measurements

In traditional regional metrics, the eigenvector centrality of the parahippocampal gyrus in PD patients was significantly reduced (d=-1.08, 95% CI 0.003-0.010, p=0.021), but no association with underlying pathology was found. The clustering coefficient showed no significant difference.

Brain Network Resilience

Advanced brain network resilience measurements indicated that the resilience of PD patients’ brain networks to dorsal anterior insula node failure was significantly reduced (d=-1.00, 95% CI 0.0012-0.0015, p=0.018). This change was not directly driven by pathology in the anterior insula or its connected regions but was associated with higher Braak α-synuclein staging (rs=-0.40, p=0.036).

Conclusion and Value

The study shows a significant reduction in brain network resilience in PD patients, particularly in response to dorsal anterior insula node failure, which is related to an increased global α-synuclein pathological burden.

Scientific Value

This study is the first to combine postmortem MRI and histopathological methods, revealing how regional topological changes and brain network resilience in brain network structure are driven by PD pathological processes.

Applied Value

The results suggest that global attention should be given to the impact of α-synuclein on PD brain network reorganization, rather than focusing solely on localized pathological processes.

Research Highlights

Key Findings

• Significant reduction in eigenvector centrality of the parahippocampal gyrus in PD patients.
• Significant reduction in brain network resilience in PD patients to dorsal anterior insula node failure.

Novelty of Research Methods

The study uses a novel approach combining postmortem MRI and histopathology, giving the results unique persuasiveness.

Pathological Drivers

The study indicates that PD brain network changes are primarily driven by a global α-synuclein pathological burden rather than localized pathological changes in specific brain regions.

Additional Content

This study was funded by the Michael J. Fox Foundation and Stichting Parkinsonfonds. We express gratitude to all brain donors and their families for their contributions, and thank all individuals who assisted with immunohistochemistry, microscopic data collection, and pathological definitions.