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dc.contributor.authorROWAN, MICHAELen
dc.date.accessioned2014-12-15T15:45:48Z
dc.date.available2014-12-15T15:45:48Z
dc.date.issued2012en
dc.date.submitted2012en
dc.identifier.citationKlyubin I, Cullen WK, Hu NW, Rowan MJ, Alzheimer's disease Aß assemblies mediating rapid disruption of synaptic plasticity and memory., Molecular brain, 5, 2012, 25en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/72481
dc.descriptionPUBLISHEDen
dc.description.abstractAlzheimer’s disease (AD) is characterized by episodic memory impairment that often precedes clinical diagnosis by many years. Probing the mechanisms of such impairment may provide much needed means of diagnosis and therapeutic intervention at an early, pre-dementia, stage. Prior to the onset of significant neurodegeneration, the structural and functional integrity of synapses in mnemonic circuitry is severely compromised in the presence of amyloidosis. This review examines recent evidence evaluating the role of amyloid-ß protein (Aβ) in causing rapid disruption of synaptic plasticity and memory impairment. We evaluate the relative importance of different sizes and conformations of Aβ, including monomer, oligomer, protofibril and fibril. We pay particular attention to recent controversies over the relevance to the pathophysiology of AD of different water soluble Aβ aggregates and the importance of cellular prion protein in mediating their effects. Current data are consistent with the view that both low-n oligomers and larger soluble assemblies present in AD brain, some of them via a direct interaction with cellular prion protein, cause synaptic memory failure. At the two extremes of aggregation, monomers and fibrils appear to act in vivo both as sources and sinks of certain metastable conformations of soluble aggregates that powerfully disrupt synaptic plasticity. The same principle appears to apply to other synaptotoxic amyloidogenic proteins including tau, α-synuclein and prion protein.en
dc.format.extent25en
dc.language.isoenen
dc.relation.ispartofseriesMolecular brainen
dc.relation.ispartofseries5en
dc.rightsYen
dc.subjectAlzheimer’s diseaseen
dc.titleAlzheimer's disease Aß assemblies mediating rapid disruption of synaptic plasticity and memory.en
dc.typeJournal Articleen
dc.contributor.sponsorEuropean Union Framework Programme 7 (FP7)en
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.contributor.sponsorHealth Research Board (HRB)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mrowanen
dc.identifier.rssinternalid92061en
dc.identifier.doihttp://dx.doi.org/10.1186/1756-6606-5-25en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumberMEMOLOAD 201159en
dc.subject.TCDThemeAgeingen
dc.subject.TCDThemeNeuroscienceen


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