Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease.

Krabbe disease, also named globoid cell (GC) leukodystrophy (GLD) for its distinct lipid-laden macrophages, is a severe leukodystrophy caused by galactosylceramidase (GALC) mutations. Hematopoietic stem cell transplant (HSCT) ameliorates disease and is associated with central nervous system (CNS) engraftment of GALC donor macrophages. Yet, the role of macrophages in GLD pathophysiology and HSCT remains unclear.