Fluid and Neuroimaging Biomarkers in Microgliopathy Colony‐Stimulating Factor‐1 Receptor‐Related Disorders

OBJECTIVE: This study aims to identify both fluid and neuroimaging biomarkers for CSF1R-RD that can inform the optimal timing of treatment administration to maximize therapeutic benefit, while also providing sensitive quantitative measurements to monitor disease progression. METHODS: Our study compared neuroimaging and fluid (plasma and cerebrospinal fluid (CSF)) biomarkers across three distinct populations: asymptomatic CSF1R pathogenic variant carriers (N = 14), symptomatic CSF1R pathogenic variant carriers (N = 17), and healthy controls (N = 30). We evaluated biomarker correlations with both an established (Montreal Cognitive Assessment (MoCA)) and a novel (CSF1R Clinical Severity Score (CCSS)) clinical diagnostic scale to investigate potential clinical utility. Additionally, we tested the relationship between select biomarkers and cortical thickness using 3D T1-weighted MPRAGE scans, providing a highly valuable physiological component to our analyses. RESULTS: Our results demonstrate that while plasma glial fibrillary acidic protein (GFAP) displays a high sensitivity for distinguishing early-stage CSF1R-RD patients from healthy controls, plasma neurofilament light chain (NfL) is more effective for tracking disease progression following the onset of symptoms. INTERPRETATION: Overall, our study provides evidence for plasma NfL and GFAP as valuable biomarkers of earliest symptom onset and disease progression for CSF1R-RD.