Systemic LPS-induced A?-solubilization and clearance in A?PP-transgenic mice is diminished by heparanase overexpression.

ABSTRACT: Amyloid-? (A?) is the main constituent of amyloid deposits in Alzheimer's disease (AD). The neuropathology is associated with neuroinflammation. Here, we investigated effects of systemic lipopolysaccharide (LPS)-treatment on neuroinflammation and A? deposition in A?PP-mice and double-transgenic mice with brain expression of A?PP and heparanase, an enzyme that degrades HS and generates an attenuated LPS-response. At 13 months of age, the mice received a single intraperitoneal injection of 50?µg LPS or vehicle, and were sacrificed 1.5 months thereafter. A? in the brain was analyzed histologically and biochemically after sequential detergent extraction. Neuroinflammation was assessed by CD45 immunostaining and mesoscale cytokine/chemokine ELISA. In single-transgenic mice, LPS-treatment reduced total A? deposition and increased Tween-soluble A?. This was associated with a reduced CXCL1, IL-1?, TNF-?-level and microgliosis, which correlated with amyloid deposition and total A?. In contrast, LPS did not change A? accumulation or inflammation marker in the double-transgenic mice. Our findings suggest that a single pro-inflammatory LPS-stimulus, if given sufficient time to act, triggers A?-clearance in A?PP-transgenic mouse brain. The effects depend on HS and heparanase.

SUBMITTER: Jendresen C 

PROVIDER: S-EPMC6418119 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature