Inflammation Disrupts Cognitive Integrity via Plasma Neurofilament Light Chain Coupling Brain Networks in Alzheimer's Disease

Background: Plasma neurofilament light chain (NFL) is a recognized biomarker for Alzheimer's disease (AD) and inflammation. Intrinsically organized default mode network core subsystem and frontoparietal network (FPN) and their interactions support complex cognitive function. The present study investigated the inflammatory effect on cognitive integrity via plasma NFL coupling internetwork interactions in AD. Objective: This study investigates the hypothesis that inflammation-related plasma NFL could affect the interactions of the core subsystem and FPN, which leads to the aggravation of the clinical symptoms of AD-spectrum patients. Methods: A total of 112 AD-spectrum participants underwent complete resting-state fMRI, neuropsychological tests, and plasma NFL at baseline (n = 112) and after approximately 17 months of follow-up (n = 112). The specific intersystem changes in the core subsystem and FPN were calculated and compared across groups. Then, the classifications of different AD-spectrum groups were analyzed using the association of plasma NFL and the changed intersystem interacting regions. Finally, mediation analysis was applied to investigate the significance of plasma NFL coupling networks on cognitive impairments in these subjects. Results: Discrimination of disease-related interactions of the core subsystem and FPN was found in AD-spectrum patients, which was the neural circuit fundamental to plasma NFL disrupting cognitive integrity. Furthermore, the clinical significance of plasma NFL coupling networks on AD identification and monitoring cognitive impairments were revealed in these subjects. Conclusion: The characteristic change in inflammation-related plasma NFL coupled with brain internetwork interactions could be used as a potential observation indicator in the progression of AD patients.