Overexpression of heparanase lowers the amyloid burden in amyloid-β precursor protein transgenic mice.

ABSTRACT: Heparan sulfate (HS) and HS proteoglycans (HSPGs) colocalize with amyloid-β (Aβ) deposits in Alzheimer disease brain and in Aβ precursor protein (AβPP) transgenic mouse models. Heparanase is an endoglycosidase that specifically degrades the unbranched glycosaminoglycan side chains of HSPGs. The aim of this study was to test the hypothesis that HS and HSPGs are active participators of Aβ pathogenesis in vivo. We therefore generated a double-transgenic mouse model overexpressing both human heparanase and human AβPP harboring the Swedish mutation (tgHpa*Swe). Overexpression of heparanase did not affect AβPP processing because the steady-state levels of Aβ1-40, Aβ1-42, and soluble AβPP β were the same in 2- to 3-month-old double-transgenic tgHpa*Swe and single-transgenic tgSwe mice. In contras

SUBMITTER: Jendresen CB 

PROVIDER: S-EPMC4335241 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature