Mutations in the human CSF1R gene impact microglia's maintenance of brain white matter integrity.

ABSTRACT: Microglia, the brain's resident macrophages, depend on interleukin-34 and colony-stimulating factor 1 (CSF1) for their development and maintenance, engaging the CSF1 receptor (CSF1R). Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a neurodegenerative disorder affecting the brain's white matter, is caused by heterozygous pathogenic mutations in the CSF1R gene. This study investigated molecular mechanisms underlying ALSP using single-nucleus RNA sequencing on postmortem brain specimens. Results showed a significant reduction in microglia in ALSP brains, with remaining cells exhibiting a unique activation signature. This reduction correlated with decreased myelinating oligodendrocytes (OLs) and increased neuropilin-2⁺ OLs with a stress-response and

SUBMITTER: Du S 

PROVIDER: S-EPMC12331135 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature