Alexander Disease (AxD)
https://onlinelibrary.wiley.com/doi/10.1002/acn3.70305
Alexander disease (AxD) is a rare genetic disorder that affects the brain and spinal cord. It is caused by changes in the GFAP gene, which leads to an abnormal build-up of a protein called glial fibrillary acidic protein (GFAP) in brain cells known as astrocytes. These cells normally support and protect neurons, but excess GFAP causes cellular stress, and the formation of structures called Rosenthal fibres, which damage the nervous system. As new therapies aim to reduce GFAP levels, it is important to understand how GFAP levels in body fluids relate to the different clinical forms of the disease. In this study, researchers measured GFAP levels in cerebrospinal fluid (CSF) and blood plasma from people with Alexander disease and compared them with individuals without the condition. The study included both single samples and repeated samples collected over time, allowing researchers to examine how GFAP levels change throughout the course of the disease. The results showed that GFAP levels were significantly higher in both CSF and blood in people with Alexander disease compared with controls. Higher levels were particularly associated with the cerebral form of the disease, which mainly affects the brain and typically presents earlier in life. The study also found that GFAP levels tend to increase in younger children, especially before the age of eight, and may decrease later in life. Interestingly, the specific genetic variant in the GFAP gene did not appear to strongly influence GFAP concentrations. Overall, these findings suggest that measuring GFAP in CSF or blood could help researchers better understand disease severity and progression. GFAP may also serve as an important biomarker in future clinical trials for emerging therapies targeting Alexander disease.