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dc.contributor.authorMcAleese, Kirsty E.
dc.contributor.authorWalker, Lauren
dc.contributor.authorGraham, Sophie
dc.contributor.authorMoya, Elisa L. J.
dc.contributor.authorJohnson, Mary
dc.contributor.authorErskine, Daniel
dc.contributor.authorColloby, Sean J.
dc.contributor.authorDey, Madhurima
dc.contributor.authorMartin-Ruiz, Carmen
dc.contributor.authorTaylor, John-Paul
dc.contributor.authorThomas, Alan J.
dc.contributor.authorMcKeith, Ian G.
dc.contributor.authorde Carli, Charles
dc.contributor.authorAttems, Johannes
dc.date.accessioned2017-07-07T14:30:12Z
dc.date.available2017-07-07T14:30:12Z
dc.date.issued2017-09
dc.identifier.citationMcAleese , K E , Walker , L , Graham , S , Moya , E L J , Johnson , M , Erskine , D , Colloby , S J , Dey , M , Martin-Ruiz , C , Taylor , J-P , Thomas , A J , McKeith , I G , de Carli , C & Attems , J 2017 , ' Parietal white matter lesions in Alzheimer’s disease are associated with cortical neurodegenerative pathology, but not with small vessel disease ' , Acta Neuropathologica , vol. 134 , no. 3 , pp. 459-473 . https://doi.org/10.1007/s00401-017-1738-2en
dc.identifier.issn0001-6322
dc.identifier.otherPURE: 250454976
dc.identifier.otherPURE UUID: 702c0ea3-7062-47b9-9445-75de5ee95092
dc.identifier.otherScopus: 85021073956
dc.identifier.otherWOS: 000407931900008
dc.identifier.urihttps://hdl.handle.net/10023/11167
dc.descriptionThe research was supported by the Alzheimer’s Society (Grant Number: AS-PG-2013-011). Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074) and by Brains for Dementia research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK.en
dc.description.abstractCerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer’s disease (AD) pathology, i.e. hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) deposition. WML seen in AD have a posterior predominance compared to non-demented individuals but it is unclear whether the pathological and molecular signatures of WML differ between these two groups. We investigated differences in the composition and aetiology of parietal WML from AD and non-demented controls. Parietal WML tissue from 55 human post-mortem brains (AD, n = 27; non-demented controls, n = 28) were quantitatively assessed for axonal loss and demyelination, as well as for cortical HPτ and Aβ burden and SVD. Biochemical assessment included Wallerian degeneration protease calpain and the myelin-associated glycoprotein (MAG) to proteolipid protein (PLP) ratio (MAG:PLP) as a measure of hypoperfusion. WML severity was associated with both axonal loss and demyelination in AD, but only with demyelination in controls. Calpain was significantly increased in WML tissue in AD, whereas MAG:PLP was significantly reduced in controls. Calpain levels were associated with increasing amounts of cortical AD-pathology but not SVD. We conclude that parietal WML seen in AD differ in their pathological composition and aetiology compared to WML seen in aged controls: WML seen in AD may be associated with Wallerian degeneration that is triggered by cortical AD-pathology, whereas WML in aged controls are due to ischaemia. Hence, parietal WML as seen on MRI should not invariably be interpreted as a surrogate biomarker for SVD as they may be indicative of cortical AD-pathology, and therefore, AD should also be considered as the main underlying cause for cognitive impairment in cases with parietal WML.
dc.format.extent15
dc.language.isoeng
dc.relation.ispartofActa Neuropathologicaen
dc.rights© The Author(s) 2017. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en
dc.subjectAlzheimer’s diseaseen
dc.subjectHyperphosphorylated tauen
dc.subjectSmall vessel diseaseen
dc.subjectWallerian degenerationen
dc.subjectWhite matter hyperintensityen
dc.subjectWhite matter lesionen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectRB Pathologyen
dc.subjectPathology and Forensic Medicineen
dc.subjectClinical Neurologyen
dc.subjectCellular and Molecular Neuroscienceen
dc.subjectNDASen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccRC0321en
dc.subject.lccRBen
dc.titleParietal white matter lesions in Alzheimer’s disease are associated with cortical neurodegenerative pathology, but not with small vessel diseaseen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.identifier.doihttps://doi.org/10.1007/s00401-017-1738-2
dc.description.statusPeer revieweden
dc.identifier.urlhttps://link.springer.com/article/10.1007%2Fs00401-017-1738-2#SupplementaryMaterialen


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