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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/124691
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dc.contributor.authorSlevin, Mark-
dc.contributor.authorSarroca, Sara-
dc.contributor.authorFont, M. Angels-
dc.contributor.authorSanfeliu, Coral-
dc.contributor.authorRevilla, Susana-
dc.contributor.authorBadimón Maestro, Lina-
dc.contributor.authorKrupinski, Jerzy-
dc.date.accessioned2015-11-09T12:28:27Z-
dc.date.available2015-11-09T12:28:27Z-
dc.date.issued2015-09-03-
dc.identifierdoi: 10.1038/srep13281-
dc.identifierissn: 2045-2322-
dc.identifier.citationScientific Reports 5: 13281 (2015)-
dc.identifier.urihttp://hdl.handle.net/10261/124691-
dc.descriptionM. Slevin et al.-
dc.description.abstractAlzheimer'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.-
dc.description.sponsorshipWe would like to thank the Fundacion BBVA for their generous support of Professor Mark Slevin through the award of BBVA Chair in Clinical Biomedicine at the ICCC, St Pau Hospital, Barcelona. This work was also supported by the Spanish Ministry of Science (SAF2009-01237 to J.K.), Spanish Ministry Project-CSD2010-00045 to C.S. and RyC (RyC2007-01466 to M.B.-P.) and the Almajmaah University Stroke Chair-
dc.publisherNature Publishing Group-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.titleMonomeric C-reactive protein - A key molecule driving development of Alzheimer's disease associated with brain ischaemia?-
dc.typeartículo-
dc.identifier.doi10.1038/srep13281-
dc.relation.publisherversionhttp://dx.doi.org/10.1038/srep13281-
dc.date.updated2015-11-09T12:28:27Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderMajmaah University-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderFundación BBVA-
dc.relation.csicSí-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100007613es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100007406es_ES
dc.identifier.pmid26335098-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.grantfulltextopen-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
item.openairetypeartículo-
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