Plasma NFL Disrupt Cognitive Integrity Via Coupling the Interactions of Core Subsystem and Frontoparietal Network in Alzheimer's Disease

Abstract

Backgroud: Plasma neurofilament light chain (NFL) is a potential biomarker for neurodegenerative diseases. Both NFL and the interactions of core subsystem and frontoparietal network (FPN) are associated with the cognitive integrity. The present study was to investigate the underlying mechanism and application of plasmaNFL couplingcore-FPN in Alzheimer’s disease (AD). Methods: A total of 224 AD-spectrum participants with complete resting-state fMRI, neuropsychological tests and plasma NFL at baseline (n=112) and after approximately 17 months follow up (n=112) . Brain networks construction of core subsystem and FPN wereperformed in these subjects. The follow-up data were used to test and verify these baseline characteristics. Furthermore, Receiver Operating Characteristic analysiswas used to explore the classification by the association of plasma NFL and core-FPN, and the mediation analysis were appliedto investigate the significance of plasma NFL coupling networks on cognitive impairments in these subjects. Results: The discernment ofdisease-relatedinteractions of core subsystem and FPN maybe the neural network fundamentals of plasmaNFL regarding to cognitive decline in AD-spectrum patients. Furthermore, the clinical significance of plasma NFL coupling networks on AD identification and monitoring cognitive impairments were observed in these subjects. Conclusions: The characteristic change of plasma NFL coupling networks could expect to be used as an potential indicator of future targeted therapies and prevention strategies in AD patients.