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

Autor:	Slevin M; School of Healthcare Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK.; University of Medicine and Pharmacy, Targu Mures, Romania.; Department of Pathology/Medicine, Griffith University, Brisbane, Australia., Matou S; School of Healthcare Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK., Zeinolabediny Y; School of Healthcare Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK., Corpas R; Instituto De Investigaciones Biomedicas De Barcelona, CSIC, Barcelona, Spain., Weston R; School of Healthcare Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK., Liu D; School of Healthcare Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK., Boras E; School of Healthcare Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK., Di Napoli M; Neurological Service, San Camillo de' Lellis General Hospital, Rieti, Italy., Petcu E; Department of Pathology/Medicine, Griffith University, Brisbane, Australia., Sarroca S; Instituto De Investigaciones Biomedicas De Barcelona, CSIC, Barcelona, Spain., Popa-Wagner A; Clinic of Neurology, Medical University Greifswald, Germany., Love S; Department of Neuropathology, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, BS16 1LE, UK., Font MA; CSIC-ICCC, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain., Potempa LA; Acphazin, Inc., Deerfield, Illinois, USA., Al-Baradie R; College of Applied Medical Science, Al Majmaah University, Majmaah City, Kingdom of Saudi Arabia P.O Box 66., Sanfeliu C; Instituto De Investigaciones Biomedicas De Barcelona, CSIC, Barcelona, Spain., Revilla S; Instituto De Investigaciones Biomedicas De Barcelona, CSIC, Barcelona, Spain., Badimon L; CSIC-ICCC, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain., Krupinski J; Hospital Universitari Mútua de Terrassa, Department of Neurology, Terrassa (Barcelona), Spain.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2015 Sep 03; Vol. 5, pp. 13281. Date of Electronic Publication: 2015 Sep 03.
DOI:	10.1038/srep13281
Abstrakt:	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.
Databáze:	MEDLINE
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