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-β (Aβ) 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 Aβ, resulting in the discovery of HS as a therapeutic drug for AD. In this manuscript, HS from porcine mucosa could promote Aβ fibrosis and improve the cognitive defects of APPswe/PS1ΔE9 mice. Furthermore, HS enhanced the phagocytosis of neutrophils to clear Aβ1-42 from peripheral circulation, reduced peripheral Aβ1-42 flow to the brain and increased Aβ efflux from the brain. Therefore, the deposition of Aβ 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.