Аннотация:Significance Keratan sulfate (KS) is an extracellular sulfated glycan covalently attached to core proteins in the brain. Here, we show that a type of KS with a certain molecular mass in microglia and its synthetic enzyme GlcNAc6ST1, previously known as a sulfotransferase for ligands of L-selectin, are upregulated in model mice and patients with Alzheimer’s disease. GlcNAc6ST1 deficiency resulted in increased amyloid-β phagocytosis and hyperresponsiveness to an antiinflammatory cytokine in primary microglia. Moreover, amyloid-β pathology was mitigated in GlcNAc6ST1-deficient Alzheimer’s model mice. These data support a model in which GlcNAc6ST1 regulates microglial functions via synthesizing sialic acid-modified KS, a potential ligand for microglial carbohydrate-recognizing receptors, in Alzheimer’s pathology.
