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Sci Rep. 2019 Mar 14;9(1):4600. doi: 10.1038/s41598-019-40999-4.

Systemic LPS-induced Aβ-solubilization and clearance in AβPP-transgenic mice is diminished by heparanase overexpression.

Author information

1
Department of Pharmacology, University of Oslo and Oslo University Hospital, Postboks 1057, Blindern, NO-0316, OSLO, Norway.
2
Department of Medical Biochemistry and Microbiology, The Biomedical Center, University of Uppsala, Box 582, SE-751 23, Uppsala, Sweden.
3
College of Life Science, Jiangxi Normal University, Nanchang, 330022, China.
4
Department of Neuroscience and Pharmacology, University of Uppsala, Box 593, SE-751 24, Uppsala, Sweden.
5
Cancer and Vascular Biology Research Center Rappaport, Faculty of Medicine, Technion, P.O. Box 9649, Haifa, 31096, Israel.
6
Department of Medical Biochemistry and Microbiology, The Biomedical Center, University of Uppsala, Box 582, SE-751 23, Uppsala, Sweden. Jin-ping.Li@imbim.uu.se.
7
Department of Pharmacology, University of Oslo and Oslo University Hospital, Postboks 1057, Blindern, NO-0316, OSLO, Norway. lars.nilsson@medisin.uio.no.

Abstract

Amyloid-β (Aβ) 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 Aβ deposition in AβPP-mice and double-transgenic mice with brain expression of AβPP 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. Aβ 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 Aβ deposition and increased Tween-soluble Aβ. This was associated with a reduced CXCL1, IL-1β, TNF-α-level and microgliosis, which correlated with amyloid deposition and total Aβ. In contrast, LPS did not change Aβ 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 Aβ-clearance in AβPP-transgenic mouse brain. The effects depend on HS and heparanase.

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