Heparan sulfate from porcine mucosa promotes amyloid-beta clearance in APP/PS1 mice and alleviates Alzheimer's pathology

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairments. Amyloid-beta (A beta) deposition and neurotoxicity play important roles in AD. It has been widely reported that heparan sulfate (HS) proteoglycans play a nonnegligible role in the release, uptake and misfolding of A beta, resulting in the discovery of HS as a therapeutic drug for AD. In this manuscript, HS from porcine mucosa could promote A beta fibrosis and improve the cognitive defects of APPswe/PS1 Delta E9 mice. Furthermore, HS enhanced the phagocytosis of neutrophils to clear A beta(1-42 )from peripheral circulation, reduced peripheral A beta(1-42 )flow to the brain and increased A beta efflux from the brain. Therefore, the deposition of A beta plaques in the brain was decreased. In addition, HS alleviated neutrophil infiltration and reduced neuroinflammation. Conclusively, HS is a promising neuroprotective candidate for AD treatment.