Mechanism of neurodegeneration mediated by clonal inflammatory microglia.

ABSTRACT: Langerhans cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD) are clonal myeloid disorders, associated with MAP-Kinase activating mutations and an increased risk of neurodegeneration. Surprisingly, we found pervasive PU.1⁺ microglia mutant clones across the brain of LCH and ECD patients with and without neurological symptoms, associated with microgliosis, reactive astrocytosis, and neuronal loss. The disease predominated in the grey nuclei of the rhombencephalon, a topography attributable to a local proliferative advantage of mutant microglia. Presence of clinical symptoms was associated with a longer evolution of the disease and a larger size of PU.1⁺ clones (p= 0.0003). Genetic lineage tracing of PU.1⁺ clones suggest a resident macrophage lineage

SUBMITTER: Vicario R 

PROVIDER: S-EPMC11312538 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature