Finally, we show that endothelial/microglial crosstalk and concomitant attenuation of CSF‐1R signalling causes re‐modelling of BBB‐associated tight junctions and suggest that regulating BBB integrity and systemic macrophage recruitment to the brain may be therapeutically relevant in ALSP and other Alzheimer’s‐like dementias. The gene discussed is CSF1R; the disease is Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia.