Anticoagulants inhibit proteolytic clearance of plasma amyloid beta

Oncotarget
Lu YangYuesheng Zhang

Abstract

We recently discovered a plasma proteolysis pathway, termed the FXII-FVII pathway which is composed of coagulation proteases, and found it to be mainly responsible for the clearance of Aβ42 in the plasma in mice. Aβ42 and Aβ40 are the main Aβ forms in Alzheimer's disease (AD). In the present study, in vitro assays, wild type (WT) mice and J20 mice (a transgenic AD model) are used to assess the degradation of Aβ40 and Aβ42 by the FXII-FVII pathway and the impact of anticoagulants on such degradation. Four clinically available and mechanistically distinct anticoagulants are evaluated, including dabigatran, enoxaparin (EP), rivaroxaban and warfarin. Each anticoagulant significantly elevates plasma level of synthetic Aβ42 in WT mice, among which EP is the most effective. The differential efficacies of the anticoagulants in elevating plasma Aβ42 level match closely with their inhibitory mechanisms towards the FXII-FVII pathway. Plasma Aβ40 is also degraded by the FXII-FVII pathway and is protected by EP. Moreover, the FXII-FVII pathway is significantly activated in J20 mice, but EP inhibits the activation and significantly elevates plasma levels of both Aβ40 and Aβ42. Taken together, our results shed new light on Aβ metabolism, reve...Continue Reading

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Citations

May 17, 2019·European Heart Journal·Leif FribergMårten Rosenqvist
Aug 18, 2020·Journal of Alzheimer's Disease : JAD·Edin BegicMirsada Causevic
Feb 3, 2019·British Journal of Pharmacology·Natalia N Nalivaeva, Anthony J Turner
Nov 6, 2020·International Journal of Cardiology·Tommy Andersson, Sara Aspberg
Mar 5, 2020·Journal of the American College of Cardiology·Dimitrios A StakosKonstantinos Stellos

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Methods Mentioned

BETA
transgenic
blood drawing
ELISA
blood draw
PCR
genotyping

Software Mentioned

GraphPad Prism

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