Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)/CSF1R related leukoencephalopathy
https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.70192
Colony-stimulating factor 1 receptor–related disorder (CSF1R‑RD) is a rare and fast‑progressing brain disease caused by harmful changes in the CSF1R gene. People with this condition can develop a wide range of symptoms, including movement problems, cognitive decline, and behavioural changes. Symptoms usually begin in the early 40s and worsen quickly, often leading to severe disability and loss of life within a few years. However, the disease varies a lot between individuals, even within the same family, suggesting that other factors may influence how it develops. This study looked at whether Apolipoprotein E (ApoE) — a gene known for affecting microglial function and playing a major role in Alzheimer’s disease — might also influence CSF1R‑RD. Researchers analysed ApoE genotypes in 55 patients and examined clinical and brain‑tissue data from smaller subgroups. They found that the overall distribution of ApoE types in CSF1R‑RD patients was similar to the general population. However, people who carried the ApoE4 variant developed symptoms much earlier and also passed earlier than those without it. Brain examinations showed that ApoE4 carriers tended to have more severe white‑matter damage and greater loss of microglia, the brain’s immune cells. These findings suggest that ApoE4 does not increase the risk of getting CSF1R‑RD, but it may make the disease progress faster and more aggressively. This means ApoE4 could act as a genetic modifier, and understanding a patient’s ApoE status may help guide diagnosis, prognosis, and future treatment strategies.