Monomeric C-reactive protein - A key molecule driving development of Alzheimer's disease associated with brain ischaemia?
Slevin, M. (Griffith University)
Matou, S. (Manchester Metropolitan University)
Zeinolabediny, Yasmin (Manchester Metropolitan University)
Corpas, Rubén (Institut d'Investigacions Biomèdiques de Barcelona)
Weston, R. (Manchester Metropolitan University)
Liu, Daijun (Manchester Metropolitan University)
Boras, E. (Manchester Metropolitan University)
Di Napoli, M. (San Camillo de' Lellis General Hospital)
Petcu, E. (Griffith University)
Sarroca, S. (Institut d'Investigacions Biomèdiques de Barcelona)
Popa-Wagner, A. (Medical University Greifswald)
Love, S. (University of Bristol)
Font, M.A. (Institut d'Investigació Biomèdica Sant Pau)
Potempa, L.A. (Acphazin Inc.)
Al-Baradie, Raid (Al Majmaah University)
Sanfeliu, C. (Institut d'Investigacions Biomèdiques de Barcelona)
Revilla, Susana (Institut d'Investigacions Biomèdiques de Barcelona)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Krupinski, J. (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Universitat Autònoma de Barcelona

Data:	2015
Resum:	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 fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spreading from infarcted core regions matched reduced expression of Aβ/Tau. mCRP may be responsible for promoting dementia after ischaemia and mCRP clearance could inform therapeutic avenues to reduce the risk of future dementia.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer Disease ; Animals ; Biomarkers ; Brain Ischemia ; Disease Progression ; Male ; Mice ; Mice, Inbred C57BL ; Neurons ; Receptors, Immunologic
Publicat a:	Scientific reports, Vol. 5 (march 2015) , p. 13281, ISSN 2045-2322

DOI: 10.1038/srep13281
PMID: 26335098

21 p, 1.8 MB

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