Nature Immunology, Published online: 26 June 2025; doi:10.1038/s41590-025-02195-7

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a neurodegenerative disorder caused by pathogenic CSF1R mutations. Here the authors find that microglial loss is linked to reduced myelinating oligodendrocytes, an expansion of neuropilin-2⁺ oligodendrocytes and a maladaptive stress response in astrocytes.



Summary

A study in Nature Immunology (June 2025) investigated adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a neurodegenerative disease caused by CSF1R mutations. The research reveals that microglial loss in ALSP is connected to a decrease in myelinating oligodendrocytes and a compensatory expansion of neuropilin-2⁺ oligodendrocytes. Furthermore, the study identifies a detrimental stress response in astrocytes as a key component of the disease pathology. These findings provide insight into the cellular mechanisms underlying ALSP and potential targets for therapeutic intervention.

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