Objective:

To assess correlation between biomarker level and clinical status of individuals with pathogenic CSF1R variants.

Background:

Colony-stimulating factor-1 receptor (CSF1R)-related disorders are rapidly progressive neurodegenerative disorder. Recent advancements have introduced potential symptomatic and prophylactic treatment options, leading to increased interest in biomarkers. These biomarkers could play a crucial role in monitoring disease progression and assessing the effectiveness of therapies.

Design/Methods:

Biomarkers were evaluated in 31 individuals with pathogenic CSF1R variants (including 17 symptomatic and 14 asymptomatic) and 30 controls. The biomarkers tested included M-CSF, IL-34, NFL, GFAP, and osteopontin in both plasma and cerebrospinal fluid (CSF).  All patients with CSF1R mutations underwent a structured neurological examination and clinical data were correlated with biomarker levels.

Results:

Plasma and CSF NFL levels were elevated in symptomatic patients compared to asymptomatic and control subjects (62.1±25.3 vs. 8.5±2.9 and 7.3±3.8 pg/ml; p>0.001 for plasma NFL and 3702.0±3107.9 pg/ml vs. 465.8±196. 7 and 537.8±321.0; p=0.0193), NFL level correlated with clinical data based on neurological examination with correlation coefficients of r=0.9759 (p<0.001) for plasma and r=0.9135 (p<0.001) for CSF level. NFL level showed strong correlation with MoCA score r=0.9005 (p<0.001) for plasma and r=0.9089 (p<0.001) for CSF level. CSF IL34 levels were higher in patients with CSF1R mutations (167.5±113 (symptomatic) and 124.2±59.6 (symptomatic) vs. 57.7±19.2pg/ml, p=0.001), similarly CSF M-CSF levels were elevated in patients with CSF1R mutations (14.0±4.38 and 8.9±2.8 vs. 5.5±1.6pg/ml; p=0.009).

Conclusions:

Plasma and CSF NFL levels appear to be reliable biomarkers for assessing clinical status and could potentially be used to monitor disease progression and treatment efficacy. Additionally, CSF IL-34 and M-CSF levels may serve as useful indicators for distinguishing between carriers of pathogenic CSF1R variants and control subjects.