Overexpression of heparanase interferes with inflammatory-associated amyloid-beta clearance in mice

• Heparan sulfate proteoglycans (HSPGs) constitutes a major component in the plaques of amyloid-beta (Aβ), and heparanase degradation of HSPGs modulates deposition of Aβ in transgenic mice overexpressing Aβ precursor protein (AβPP) harboring Swedish mutation (tgSwe). In this study, we examined implications of heparanase expression in resolving/clearance of deposited Aβ in the tgSwe mice using an inflammation model induced by LPS-stimulation. Immunohistological staining of Aβx-40 and Aβx-42 showed reduced Aβ-burden in the brain of LPS-stimulated tgSwe in comparison to vehicle treated tgSwe. This reduction of Aβ-burden was evidenced by a significant decrease in the SDS and formic acid soluble Aβ in the brain lysate. In comparison, LPS-treatment had a marginal effect on Aβ-burden in the double transgenic (tgHpa*Swe) mice overexpressing both human heparanase and human AβPP. An immunological array analysis revealed an overall lower level of the inflammatory cytokines examined in the brain lysates of tgHpa*Swe mice, suggesting that heparanase overexpression attenuated inflammatory-associated clearance of deposited Aβ.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Alzheimer's disease

APP mouse

Heparanase

Heparan sulfate

Neuroinflammation

Amyloidosis

Clearance

A beta

Neurology

Neurologi

Publication and Content Type

vet (subject category)

ovr (subject category)