Monomeric C-reactive protein--a key molecule driving development of Alzheimer's disease associated with brain ischaemia?

Scientific Reports
Mark SlevinJerzy Krupinski

Abstract

Alzheimer's disease (AD) increases dramatically in patients with ischaemic stroke. Monomeric C-reactive protein (mCRP) appears in the ECM of ischaemic tissue after stroke, associating with microvasculature, neurons and AD-plaques, Aβ, also, being able to dissociate native-CRP into inflammatory, mCRP in vivo. Here, mCRP injected into the hippocampal region of mice was retained within the retrosplenial tract of the dorsal 3rd ventrical and surrounding major vessels. Mice developed behavioural/cognitive deficits within 1 month, concomitant with mCRP staining within abnormal looking neurons expressing p-tau and in beta-amyloid 1-42-plaque positive regions. mCRP co-localised with CD105 in microvessels suggesting angiogenesis. Phospho-arrays/Western blotting identified signalling activation in endothelial cells and neurons through p-IRS-1, p-Tau and p-ERK1/2-which was blocked following pre-incubation with mCRP-antibody. mCRP increased vascular monolayer permeability and gap junctions, increased NCAM expression and produced haemorrhagic angiogenesis in mouse matrigel implants. mCRP induced tau244-372 aggregation and assembly in vitro. IHC study of human AD/stroke patients revealed co-localization of mCRP with Aβ plaques, tau-like fibr...Continue Reading

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Apr 25, 2017·Scientific Reports·Yingying HuangYongxiang Zhao
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Methods Mentioned

BETA
transfection
PCR
electrophoresis
Antibody Microarray
protein assay
transgenic

Software Mentioned

Primer3
Elements
SPSS
Kinexus
Nis
Image
Kinetworks
Kinexus Bioinformatics

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