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dc.contributor.authorBOKDE, ARUN LAWRENCE WARREN
dc.contributor.authorBEDE, PETER
dc.contributor.authorHAMPEL, HARALD
dc.contributor.authorHARDIMAN, ORLA
dc.date.accessioned2012-01-12T15:15:16Z
dc.date.available2012-01-12T15:15:16Z
dc.date.issued2011
dc.date.submitted2011en
dc.identifier.citationF. Geser, L. O'Dwyer, O. Hardiman, P. Bede, A.L.W. Bokde, D. Prvulovic, John Q. Trojanowski, H. Hampel, On the development of markers for pathological TDP-43 in amyotrophic lateral sclerosis with and without dementia, Progress in Neurobiology, 95, 4, 2011, 649 662en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/61636
dc.descriptionPUBLISHEDen
dc.description.abstractPathological 43-kDa transactive responsive sequence DNA-binding protein (TDP-43) has been recognized as the major disease protein in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin positive, tau and ?-synuclein negative inclusions (FTLD-U) and the transitional forms between these multisystem conditions. In order to develop TDP-43 into a successful ALS biomarker, the natural history of TDP-43 pathology needs to be characterized and the underlying pathophysiology established. Here we propose a spatial and temporal ?two-axis? model of central nervous system vulnerability for TDP-43 linked degeneration and discuss recent studies on potential biomarkers related to pathological TDP-43 in the cerebrospinal fluid (CSF), blood, and skeletal muscle. The model includes the following ?two arms?: First, a ?motor neuron disease? or ?spinal cord/brainstem to motor cortex? axis (with degeneration possibly ascending from the lower motor neurons to the upper motor neurons); and secondly, a ?dementia? or ?corticoid/allocortical to neocortex? axis (with a probable spread of TDP-43 linked degeneration from the mediotemporal lobe to wider mesocortical and neocortical brain areas). At the cellular level, there is a gradual disappearance of normal TDP-43 in the nucleus in combination with the formation of pathological aggregates in the cell body and cellular processes, which can also be used to identify the stage of the disease process. Moreover, TDP-43 lesions in subpial/subependymal or perivascular localizations have been noted in TDP-43 linked neurodegeneration, and this might account for increased CSF and blood TDP-43 levels through mechanisms that remain to be elucidated.en
dc.format.extent649 662en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.ispartofseriesProgress in Neurobiology;
dc.relation.ispartofseries95;
dc.relation.ispartofseries4;
dc.rightsYen
dc.subjectNeuroscienceen
dc.subjectAmyothrophic lateral sclerosisen
dc.titleOn the development of markers for pathological TDP-43 in amyotrophic lateral sclerosis with and without dementiaen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/hampel
dc.identifier.peoplefinderurlhttp://people.tcd.ie/bokdea
dc.identifier.peoplefinderurlhttp://people.tcd.ie/pbede
dc.identifier.peoplefinderurlhttp://people.tcd.ie/hardimao
dc.identifier.rssinternalid74842
dc.identifier.rssurihttp://dx.doi.org/10.1016/j.pneurobio.2011.08.011en


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