Single nucleus analysis of post-mortem brain tissues from Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) patients

Microglia, the brain's resident macrophages, depend on interleukin 34 (IL-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. Neuropathological studies of postmortem ALSP brains have shown widespread depletion of microglia, demyelination of cerebral white matter, axonal swellings, and pigmented glial cells. In this study, we investigated how individual brain cell populations respond to microglia depletion and contribute to ALSP progression. To do this, we analyzed post-mortem specimens from patients wirth ALSP using single-nucleus RNA-seq (snRNA-seq).