Deficiency of a sulfotransferase for sialic acid-modified glycans mitigates Alzheimer's pathology.

ABSTRACT: We previously showed that microglial keratan sulfate (KS) was induced in amyotrophic lateral sclerosis. However, the functional roles of the glycan and its synthetic enzyme in neurodegenerative diseases, such as Alzheimer's disease (AD), a progressive disorder, are unclear. In our study, KS modified with sialic acids having a molecular mass of 125-220 kDa and the carbohydrate sulfotransferase GlcNAc6ST1 were up-regulated in the brains of two transgenic mouse models (J20 and Tg2576) and the brains of patients with AD. GlcNAc6ST1-deficient J20 (J20/GlcNAc6ST1^-/-) mice demonstrated a complete absence of the microglial sialylated KS. J20/GlcNAc6ST1^-/- primary microglia showed an increased level of amyloid-β phagocytosis and were hyperresponsive to interleukin 4, a potent

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC5389269 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature