Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)/CSF1R related leukoencephalopathy
https://onlinelibrary.wiley.com/doi/10.1002/acn3.70250
Colony-stimulating factor 1 receptor–related disorder (CSF1R-RD) is a rare inherited neurodegenerative disease caused by changes in the CSF1R gene, which is essential for the health of microglia. People with CSF1R-RD typically develop progressive problems with thinking, behaviour, and movement in mid-adulthood, and the disease advances rapidly. Diagnosis is often delayed or mistaken, and there is an urgent need for reliable biomarkers to detect early disease and monitor progression, especially as potential treatments are emerging. The aim of this study was to find blood and brain imaging markers for CSF1R-RD that can help determine the best time to start treatment and track how the disease progresses. In this study, the researchers examined blood, cerebrospinal fluid, and brain MRI biomarkers in 31 individuals carrying CSF1R variants (14 asymptomatic and 17 symptomatic) and compared them with healthy controls (30 individuals). The correlation between these biomarkers were evaluated using an established (Montreal Cognitive Assessment (MoCA)) and newly developed (CSF1R Clinical Severity Score (CCSS)) diagnostic scale to capture the full range of symptoms. Brain imaging confirmed marked white-matter damage and brain atrophy in symptomatic individuals, which closely correlated with cognitive impairment and clinical severity. From the data captured, two blood biomarkers stood out to the researchers. Glial fibrillary acidic protein (GFAP), a marker of astrocyte and glial stress, was already elevated in some individuals before symptoms began, making it a promising indicator of the earliest disease changes. In contrast, neurofilament light chain (NfL), a marker of axonal injury, rose sharply after symptom onset and closely tracked disease severity, brain tissue loss, and clinical decline. Together, these findings suggest that GFAP and NfL offer complementary insights: GFAP can help detect the very earliest stages of disease, while NfL effectively tracks disease progression and response to treatment. These results highlight the importance of incorporating both biomarkers into future diagnostic and monitoring strategies for CSF1R-RD.