A hallmark of Alzheimer’s disease (AD) is deposition of the amyloid-β (Aβ) in the brain parenchyma, which is caused by either overproduction (genetic mutations) or deficiency in clearance. Defective amyloid-β (Aβ) clearance from the brain is a major contributing factor to the majority of sporadic cases, typically associated with cerebral amyloid angiopathy due to perivascular accumulation of Ab. Heparan sulfate (HS) is an important component of blood vessels and vascular basement membrane (VBM), having important functions in maintaining the BBB integrity. Using mouse models, our study revealed the critical roles of HS in perivascular drainage. Overexpression of heparanase resulted in thicker VBMs and swollen perivascular astrocyte endfeet, leading to defect in the perivascular clearance of intracortical injected Aβ. Elevated heparanase was also detected in human AD brain. The findings suggest a potential role for heparanase in the pathogenesis of AD, through increased fragmentation of BBB-associated HS, resulting in defective perivascular drainage.

Heparanase overexpression impedes perivascular clearance of amyloid-b from murine brain - relevance to Alzheimer’s disease

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.